Hypertension On-line First

Noninvasive Assessment of Arterial Stiffness Should Discriminate Between Systolic and Diastolic Pressure Ranges [Scientific Contributions]

Mon, 23 Nov 2009 13:01:07 PST

Abstract—Arterial stiffening plays an important role in the development of hypertension and cardiovascular diseases. The intrinsically nonlinear (ie, pressure-dependent) elastic behavior of arteries may have serious consequences for the accuracy and interpretation of arterial stiffness measurements and, ultimately, for individual patient management. We determined aortic pressure and common carotid artery diameter waveforms in 21 patients undergoing cardiac catheterization. The individual pressure-area curves were described using a dual exponential analytic model facilitating noise-free calculation of incremental pulse wave velocity. In addition, compliance coefficients were calculated separately in the diastolic and systolic pressure ranges, only using diastolic, dicrotic notch, and systolic data points, which can be determined noninvasively. Pulse wave velocity at systolic pressure exhibited a much stronger positive correlation with pulse pressure (P<0.001) and age (P=0.012) than pulse wave velocity at diastolic pressure. Patients with an elevated systolic blood pressure (>140 mm Hg) had a 2.5-times lower compliance coefficient in the systolic pressure range than patients with systolic blood pressures <140 mm Hg (P=0.002). Most importantly, some individuals, with comparable age or pulse pressure, had similar diastolic but discriminately different systolic pulse wave velocities and compliance coefficients. We conclude that noninvasive assessment of arterial stiffness could and should discriminate between systolic and diastolic pressure ranges to more precisely characterize arterial function in individual patients.

A Translational Approach to Hypertensive Heart Disease [Brief Reviews]

Diez, J., Frohlich, E. D. — Mon, 23 Nov 2009 13:00:45 PST

Evidence for the Importance of Adiponectin in the Cardioprotective Effects of Pioglitazone [Scientific Contributions]

Mon, 23 Nov 2009 13:00:26 PST

Abstract—The favorable effects of the peroxisome proliferator-activated receptor- ligand pioglitazone on glucose metabolism are associated with an increase in the fat-derived hormone adiponectin in the bloodstream. A recent clinical trial, Prospective Pioglitazone Clinical Trial in Macrovascular Events, demonstrated that pioglitazone improved cardiovascular outcomes in patients with type 2 diabetes mellitus. However, the functional role of adiponectin in cardioprotection by pioglitazone has not been examined experimentally. Here we investigated the effect of pioglitazone on angiotensin II (Ang II)–induced cardiac hypertrophy and assessed the potential contribution of adiponectin to the action of pioglitazone on the heart. Wild-type or adiponectin-deficient mice were treated with pioglitazone as food admixture at a concentration of 0.01% for 1 week followed by 2 weeks of infusion with Ang II at 3.2 mg/kg per day. Ang II infusion in wild-type mice resulted in exacerbated myocyte hypertrophy and increased interstitial fibrosis, which were accompanied by elevated phosphorylation of extracellular signal-regulated kinase and expression of transforming growth factor-β1 in the heart. Treatment of wild-type mice with pioglitazone attenuated cardiac hypertrophy and fibrosis, extracellular signal-regulated kinase phosphorylation, and transforming growth factor-β1 expression in response to Ang II. Pioglitazone also increased the plasma adiponectin level and phosphorylation of cardiac AMP-activated protein kinase in wild-type mice in the presence of Ang II. The suppressive effects of pioglitazone on Ang II–induced cardiac hypertrophy and fibrosis were diminished in adiponectin-deficient mice. Furthermore, pioglitazone had no effects on the phosphorylation of extracellular signal-regulated kinase and AMP-activated protein kinase in the Ang II–infused heart of adiponectin-deficient mice. These data provide direct evidence that pioglitazone protects against Ang II–induced pathological cardiac remodeling via an adiponectin-dependent mechanism.

Within-Patient Reproducibility of the Aldosterone:Renin Ratio in Primary Aldosteronism [Scientific Contributions]

Mon, 23 Nov 2009 13:00:13 PST

Abstract—The plasma aldosterone concentration:renin ratio (ARR) is widely used for the screening of primary aldosteronism, but its reproducibility is unknown. We, therefore, investigated the within-patient reproducibility of the ARR in a prospective multicenter study of consecutive hypertensive patients referred to specialized centers for hypertension in Italy. After the patients were carefully prepared from the pharmacological standpoint, the ARR was determined at baseline in 1136 patients and repeated after, on average, 4 weeks in the patients who had initially an ARR ≥40 and in 1 of every 4 of those with an ARR <40. The reproducibility of the ARR was assessed with Passing and Bablok and Deming regression, coefficient of reproducibility, and Bland-Altman and Mountain plots. Within-patient ARR comparison was available in 268 patients, of whom 49 had an aldosterone-producing adenoma, on the basis of the "4-corner criteria." The ARR showed a highly significant within-patient correlation (r=0.69; P<0.0001) and reproducibility. Bland-Altman plot showed no proportional, magnitude-related, or absolute systematic error between the ARR; moreover, only 7% of the values, for example, slightly more than what could be expected by chance, fell out of the 95% CI for the between-test difference. The accuracy of each ARR for pinpointing aldosterone-producing adenoma patients was 80%. Thus, although it was performed under different conditions in a multicenter study, the ARR showed a good within-patient reproducibility. Hence, contrary to previously claimed poor reproducibility of the ARR, these data support its use for the screening of primary aldosteronism.

Aortic Stiffness, Impaired Fasting Glucose, and Aging [Editorial Commentaries]

Dietrich, T., Schaefer-Graf, U., Fleck, E., Graf, K. — Mon, 23 Nov 2009 13:00:00 PST

Modification of the Effect of Glycemic Status on Aortic Distensibility by Age in the Multi-Ethnic Study of Atherosclerosis [Scientific Contributions]

Mon, 23 Nov 2009 12:59:46 PST

Abstract—Elevated serum glucose from diabetes mellitus (DM) or impaired fasting glucose shares many mechanisms with aging that decrease aortic distensibility (AD), such as glycation of the extracellular matrix. However, few data compare the simultaneous effects of elevated serum glucose and aging on AD. To study this, we examined the relationship among fasting glucose status, age, and AD in the Multi-Ethnic Study of Atherosclerosis: a multiethnic cohort of individuals aged 45 to 84 years without clinical cardiovascular disease. In the Multi-Ethnic Study of Atherosclerosis, participants with normal fasting glucose (n=2270), impaired fasting glucose (n=870), and DM (n=412) underwent MRI assessment of proximal thoracic aortic distensibility. This sample was 46% male, 42% white, 30% black, 11% Asian, and 17% Hispanic. The relationship among glucose status, age, and AD was analyzed with general linear models by adjusting for factors influential on AD. An interaction term was used to determine whether age modified the effect of glucose status on AD. AD was lowest among those with DM. The interaction term was significant (P=0.024). Comparing participants <65 years of age, AD was different between normal fasting glucose and DM (P<0.01) and between normal fasting glucose and impaired fasting glucose (P=0.02). In those >65 years of age, the fasting glucose group was no longer a significant predictor of AD. Our data indicate that there are overall differences in AD among DM, impaired fasting glucose, and normal fasting glucose. However, age modified the effect of glucose status such that differences between the groups diminished with advancing age.

Both the Toolset and Motivation Are Needed for Lasting Change [Editorial Commentaries]

Taler, S. J. — Tue, 17 Nov 2009 06:50:25 PST

Hypertension Improvement Project. Randomized Trial of Quality Improvement for Physicians and Lifestyle Modification for Patients [Scientific Contributions]

Tue, 17 Nov 2009 06:50:09 PST

Abstract—Despite widely publicized hypertension treatment guidelines for physicians and lifestyle recommendations for patients, blood pressure control rates remain low. In community-based primary care clinics, we performed a nested, 2x2 randomized, controlled trial of physician intervention versus control and/or patient intervention versus control. Physician intervention included internet-based training, self-monitoring, and quarterly feedback reports. Patient intervention included 20 weekly group sessions followed by 12 monthly telephone counseling contacts and focused on weight loss, Dietary Approaches to Stop Hypertension dietary pattern, exercise, and reduced sodium intake. The primary outcome was change in systolic blood pressure at 6 months. Eight primary care practices (32 physicians) were randomized to physician intervention or control groups. Within those practices, 574 patients were randomized to patient intervention or control groups. Patient mean age was 60 years, 61% were women, and 37% were black. Blood pressure data were available for 91% of patients at 6 months. The main effect of physician intervention on systolic blood pressure at 6 months, adjusted for baseline pressure, was 0.3 mm Hg (95% CI: -1.5 to 2.2; P=0.72). The main effect of the patient intervention was -2.6 mm Hg (95% CI: -4.4 to -0.7; P=0.01). The interaction of the 2 interventions was significant (P=0.03); the largest impact was observed with the combination of physician and patient intervention (-9.7±12.7 mm Hg). Differences between treatment groups did not persist at 18 months. Combined physician and patient interventions lowers blood pressure; future research should focus on enhancing effectiveness and sustainability of these interventions.

Thiazide Diuretics Alone or With {beta}-Blockers Impair Glucose Metabolism in Hypertensive Patients With Abdominal Obesity [Editorial Commentaries]

Manrique, C., Johnson, M., Sowers, J. R. — Mon, 16 Nov 2009 12:56:08 PST

Impact of Abdominal Obesity on Incidence of Adverse Metabolic Effects Associated With Antihypertensive Medications [Scientific Contributions]

Mon, 16 Nov 2009 12:55:54 PST

Abstract—We assessed adverse metabolic effects of atenolol and hydrochlorothiazide among hypertensive patients with and without abdominal obesity using data from a randomized, open-label study of hypertensive patients without evidence of cardiovascular disease or diabetes mellitus. Intervention included randomization to 25 mg of hydrochlorothiazide or 100 mg of atenolol monotherapy followed by their combination. Fasting glucose, insulin, triglycerides, high-density lipoprotein cholesterol, and uric acid levels were measured at baseline and after monotherapy and combination therapy. Outcomes included new occurrence of and predictors for new cases of glucose ≥100 mg/dL (impaired fasting glucose), triglyceride ≥150 mg/dL, high-density lipoprotein ≤40 mg/dL for men or ≤50 mg/dL for women, or new-onset diabetes mellitus according to the presence or absence of abdominal obesity. Abdominal obesity was present in 167 (58%) of 395 patients. Regardless of strategy, in those with abdominal obesity, 20% had impaired fasting glucose at baseline compared with 40% at the end of study (P<0.0001). Proportion with triglycerides ≥150 mg/dL increased from 33% at baseline to 46% at the end of study (P<0.01). New-onset diabetes mellitus occurred in 13 patients (6%) with and in 4 patients (2%) without abdominal obesity. Baseline levels of glucose, triglyceride, and high-density lipoprotein predicted adverse outcomes, and predictors for new-onset diabetes mellitus after monotherapy in those with abdominal obesity included hydrochlorothiazide strategy (odds ratio: 46.91 [95% CI: 2.55 to 862.40]), female sex (odds ratio: 31.37 [95% CI: 2.10 to 468.99]), and uric acid (odds ratio: 3.19 [95% CI: 1.35 to 7.52]). Development of adverse metabolic effect, including new-onset diabetes mellitus associated with short-term exposure to hydrochlorothiazide and atenolol was more common in those with abdominal obesity.

Sex Differences in Pulse Pressure Trends With Age Are Cross-Cultural [Scientific Contributions]

Skurnick, J. H., Aladjem, M., Aviv, A. — Mon, 16 Nov 2009 12:55:38 PST

Abstract—Sex differences in systolic and diastolic blood pressure levels and trends with age have been consistently observed in both industrialized and unindustrialized populations. However, the impact of sex on pulse pressure, an index of vascular aging, in unindustrialized populations has not been addressed. The objective of this report was to characterize sex differences in aging trends of pulse pressure within unindustrialized populations. Using PubMed and Medline, we identified 60 articles with blood pressure data from unacculturated or partially acculturated populations. Data on 27 populations from 22 articles were included for analysis, on the basis of adequate description of study design and blood pressure measurement. Blood pressure means of adult age groups were modeled by linear and polynomial regression. The pulse pressure levels of women were lower than those of men in early adulthood and higher in older ages. Women had a steeper, steady increase in pulse pressure with age than men (P<0.001), whereas men had a stronger curvilinear upswing in pulse pressure with age (P=0.006). Partially acculturated populations had higher pulse pressures than unacculturated populations. Sex had a stronger effect on pulse pressure than acculturation. Pulse pressure trajectories of unindustrialized populations were slightly attenuated compared with those seen in National Health and Nutritional Examination Surveys III and IV of the US population. A sex effect on pulse pressure trends with age prevails across unacculturated and acculturated populations. Accordingly, the biological principles of arterial aging, as expressed in pulse pressure, are the same in all humans, regardless of demography.

Aliskiren Monotherapy Does Not Cause Paradoxical Blood Pressure Rises. Meta-Analysis of Data From 8 Clinical Trials [Scientific Contributions]

Mon, 16 Nov 2009 12:55:20 PST

Abstract—Angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and diuretics all cause reactive rises in plasma renin concentration, but particularly high levels have been reported with aliskiren. This prompted speculation that blockade of plasma renin activity with aliskiren could be overwhelmed, leading to paradoxical increases in blood pressure. This meta-analysis of data from 4877 patients from 8 randomized, double-blind, placebo- and/or active-controlled trials examined this hypothesis. The analysis focused on the incidence of paradoxical blood pressure increases above predefined thresholds, after ≥4 weeks of treatment with 300 mg of aliskiren, angiotensin receptor blockers (300 mg of irbesartan, 100 mg of losartan, or 320 mg of valsartan), 10 mg of ramipril, 25 mg of hydrochlorothiazide, or placebo. There were no significant differences in the frequency of increases in systolic (>10 mm Hg; P=0.30) or diastolic (>5 mm Hg; P=0.65) pressure among those treated with aliskiren (3.9% and 3.1%, respectively), angiotensin receptor blockers (4.0% and 3.7%), ramipril (5.7% and 2.6%), or hydrochlorothiazide (4.4% and 2.7%). Increases in blood pressure were considerably more frequent in the placebo group (12.6% and 11.4%; P<0.001). None of the 536 patients with plasma renin activity data who received 300 mg of aliskiren exhibited an increase in systolic pressure >10 mm Hg that was associated with an increase in plasma renin activity >0.1 ng/mL per hour. In conclusion, the incidence of blood pressure increases with aliskiren was similar to that during treatment with other antihypertensive drugs. Blood pressure rises on aliskiren treatment were not associated with increases in plasma renin activity. This meta-analysis found no evidence that aliskiren uniquely causes paradoxical rises in blood pressure.

Lack of Glutathione Peroxidase 1 Accelerates Cardiac-Specific Hypertrophy and Dysfunction in Angiotensin II Hypertension [Scientific Contributions]

Mon, 16 Nov 2009 12:55:04 PST

Abstract—Glutathione peroxidase 1 (Gpx1) plays an important role in cellular defense by converting hydrogen peroxide and organic hydroperoxides to nonreactive products, and Gpx1^-/- mice, which are characterized by reduced tissue glutathione peroxidase activity, are known to exhibit enhanced oxidative stress. Peroxides participate in tissue injury, as well as the hypertrophy of cultured cells, yet the role of Gpx1 to prevent end organ damage in cardiovascular tissue is not clear. We postulated that Gpx1 deletion would potentiate both aortic and cardiac hypertrophy, as well as mean arterial blood pressure, in response to angiotensin II (AngII). Our results show that short-term AngII markedly increased left ventricular mass, myocyte cross-sectional area, and interventricular septum thickness and decreased shortening fraction in Gpx1^-/- mice as compared with wild-type animals. On the other hand, AngII resulted in a similar increase in mean arterial blood pressure in wild-type and Gpx1^-/- mice. Collagen deposition increased in response to AngII, but no differences were found between strains. Vascular hypertrophy increased to the same extent in Gpx1^-/- and wild-type mice. Collectively, our results indicate that Gpx1 deficiency accelerates cardiac hypertrophy and dysfunction but has no effect on vascular hypertrophy and mean arterial blood pressure and suggest a major role for Gpx1 in cardiac dysfunction in AngII-dependent hypertension.

p21-Activated Kinase 1 Participates in Vascular Remodeling In Vitro and In Vivo. Inter-American Society of Hypertension [Scientific Contributions]

Mon, 09 Nov 2009 12:51:27 PST

Abstract—Vascular smooth muscle cell hypertrophy, proliferation, or migration occurs in hypertension, atherosclerosis, and restenosis after angioplasty, leading to pathophysiological vascular remodeling. Angiotensin II and platelet-derived growth factor are well-known participants of vascular remodeling and activate a myriad of downstream protein kinases, including p21-activated protein kinase (PAK1). PAK1, an effector kinase of small GTPases, phosphorylates several substrates to regulate cytoskeletal reorganization. However, the exact role of PAK1 activation in vascular remodeling remains to be elucidated. Here, we have hypothesized that PAK1 is a critical target of intervention for the prevention of vascular remodeling. Adenoviral expression of dominant-negative PAK1 inhibited angiotensin II–stimulated vascular smooth muscle cell migration. It also inhibited vascular smooth muscle cell proliferation induced by platelet-derived growth factor. PAK1 was activated in neointima of the carotid artery after balloon injury in the rat. Moreover, marked inhibition of the neointima hyperplasia was observed in a dominant-negative PAK1 adenovirus-treated carotid artery after the balloon injury. Taken together, these results suggest that PAK1 is involved in both angiotensin II and platelet-derived growth factor–mediated vascular smooth muscle cell remodeling, and inactivation of PAK1 in vivo could be effective in preventing pathophysiological vascular remodeling.

Mitogen-Activated Protein Kinases as Biomarkers of Hypertension or Cardiac Pressure Overload [Editorial Commentaries]

Ocaranza, M. P., Jalil, J. E. — Mon, 09 Nov 2009 12:51:06 PST

Sympathetic Tone in the Young. The Mother Weighs In [Editorial Commentaries]

Rahmouni, K. — Mon, 09 Nov 2009 12:50:51 PST

Extracellular Signal-Regulated Kinase 1/2 Activation, via Downregulation of Mitogen-Activated Protein Kinase Phosphatase 1, Mediates Sex Differences in Desoxycorticosterone Acetate-Salt Hypertension Vascular Reactivity. Inter-American Society of Hypertension [Scientific Contributions]

Mon, 09 Nov 2009 12:50:37 PST

Abstract—Extracellular signal–regulated kinase (ERK)1/2 has been reported to play a role in vascular dysfunction associated with mineralocorticoid hypertension. We hypothesized that, compared with female rats, an upregulation of ERK1/2 signaling in the vasculature of male rats contributes to augmented contractile responses in mineralocorticoid hypertension. Uninephrectomized male and female Sprague-Dawley rats received desoxycorticosterone acetate (DOCA) pellets (200 mg per animal) and saline to drink for 3 weeks. Control uninephrectomized rats received tap water to drink. Blood pressure, measured by telemetry, was significantly higher in male DOCA rats (191±3 mm Hg) compared with female DOCA rats (172±7 mm Hg; n=5). DOCA treatment resulted in augmented contractile responses to phenylephrine in aorta (22±3 mN; n=6) and small mesenteric arteries (13±2 mN; n=6) from male DOCA rats versus uninephrectomized male rats (16±3 and 10±2 mN, respectively; P<0.05) and female DOCA rats (15±1 and 11±1 mN, respectively). ERK1/2 inhibition with PD-98059 (10 µmol/L) abrogated increased contraction to phenylephrine in aorta (14±2 mN) and small mesenteric arteries (10±2 mN) from male DOCA rats, without any effects in arteries from male uninephrectomized or female animals. Compared with the other groups, phosphorylated ERK1/2 levels were increased in the aorta from male DOCA rats, whereas mitogen-activated protein kinase phosphatase 1 expression was decreased. Interleukin-10 plasma levels, which positively regulate mitogen-activated protein kinase phosphatase 1 activity, were reduced in male DOCA-salt rats. We speculate that augmented vascular reactivity in male hypertensive rats is mediated via activation of the ERK1/2 pathway. In addition, mitogen-activated protein kinase phosphatase 1 and interleukin 10 play regulatory roles in this process.

Evidence for Sympathetic Origins of Hypertension in Juvenile Offspring of Obese Rats [Scientific Contributions]

Mon, 09 Nov 2009 12:50:21 PST

Abstract—Maternal obesity in rodents is associated with increased adiposity, impaired glucose tolerance, and hypertension in adult offspring. In this study we investigated the influence of maternal obesity in the rat on blood pressure and blood pressure regulatory pathways in juvenile and adult offspring. Obesity was induced before pregnancy in female Sprague-Dawley rats by feeding a highly palatable energy-dense diet. In juvenile animals (30 days of age), before the onset of obesity and hyperleptinemia, basal nighttime mean arterial pressure was significantly raised in the offspring of obese dams (OffOb) relative to offspring of controls (OffCon; mean arterial pressure, males: OffOb, 121.8±0.6 mm Hg versus OffCon, 115.0±0.5 mm Hg, n=6, P<0.01; females: OffOb, 125.4±0.4 mm Hg versus OffCon, 114.4±0.5 mm Hg, n=6, P<0.001), as was the mean arterial pressure response to restraint stress (P<0.01). The pressor response to a leptin challenge was enhanced in OffOb rats (mean arterial pressure: OffOb, 9.7±0.8 mm Hg versus OffCon, 5.3±1.3 mm Hg; n=8; P<0.05). Renal tissue norepinephrine content (P<0.001) and renin expression (P<0.05) were markedly raised. Analysis of heart rate variability revealed an increased low:high frequency ratio in OffOb versus OffCon rats (P<0.05). At 90 days, hypertension in OffOb rats persisted and was abolished by 1- and β-adrenergic blockade, and cardiovascular responses to phenylephrine or sodium nitroprusside indicated altered baroreceptor function. The exaggerated pressor response to leptin in OffOb rats was maintained. Hypertension in the offspring of obese rats may arise from persistent sympathoexcitatory hyperresponsiveness acquired in early stages of development.

Induction of Mitogen-Activated Protein Kinases Is Proportional to the Amount of Pressure Overload [Scientific Contributions]

Mon, 09 Nov 2009 12:50:08 PST

Abstract—Pressure overload has been shown to induce mitogen activated protein kinases (MAPKs) and reactivate the atrial natriuretic factor in the heart. To test the sensitivity of these signals to pressure overload, we assayed the activity of MAPKs extracellular signal–regulated kinase, c-Jun N-terminal kinase 1, and p38 in protein lysates from the left ventricle (LV) or white blood cells (WBC) isolated from aortic banded mice with varying levels of pressure overload. In separated mice we measured atrial natriuretic factor mRNA levels by Northern blotting. As expected, a significant induction of atrial natriuretic factor mRNA levels was observed after aortic banding, and it significantly correlated with the trans-stenotic systolic pressure gradient but not with the LV weight:body weight ratio. In contrast, a significant correlation with systolic pressure gradient or LV weight:body weight ratio was observed for all of the MAPK activity detected in LV samples or WBCs. Importantly, LV activation of MAPKs significantly correlated with their activation in WBCs from the same animal. To test whether MAPK activation in WBCs might reflect uncontrolled blood pressure levels in humans, we assayed extracellular signal–regulated kinase, c-Jun N-terminal kinase 1, and p38 activation in WBCs isolated from normotensive volunteers, hypertensive patients with controlled blood pressure values, or hypertensive patients with uncontrolled blood pressure values. Interestingly, in hypertensive patients with controlled blood pressure values, LV mass and extracellular signal–regulated kinase phosphorylation were significantly reduced compared with those in hypertensive patients with uncontrolled blood pressure values. These results suggest that MAPKs are sensors of pressure overload and that extracellular signal–regulated kinase activation in WBCs might be used as a novel surrogate biomarker of uncontrolled human hypertension.

Efficacy of Spironolactone Therapy in Patients With True Resistant Hypertension. Inter-American Society of Hypertension [Scientific Contributions]

de Souza, F., Muxfeldt, E., Fiszman, R., Salles, G. — Mon, 26 Oct 2009 12:52:49 PDT

Abstract—The role of spironolactone in resistant hypertension management is unclear. The aim of this prospective trial was to evaluate the antihypertensive effect of spironolactone in patients with true resistant hypertension diagnosed by ambulatory blood pressure monitoring. A total of 175 patients had clinical and complementary exams obtained at baseline and received spironolactone in doses of 25 to 100 mg/d. A second ambulatory blood pressure monitoring was performed after a median interval of 7 months. Paired Student t test was used to assess differences in blood pressure before and during spironolactone administration, and multivariate analysis adjusted for age, sex, and number of antihypertensive drugs to assess the predictors of blood pressure fall. There were mean reductions of 16 and 9 mm Hg, respectively, in 24-hour systolic and diastolic blood pressures (95% CIs: 13 to 18 and 7 to 10 mm Hg; P<0.001). Office systolic blood pressure and diastolic blood pressure also decreased (14 and 7 mm Hg). Controlled ambulatory blood pressure was reached in 48% of patients. Factors associated with better response were higher waist circumference, lower aortic pulse wave velocity, and lower serum potassium. No association with plasma aldosterone or aldosterone:renin ratio was found. Adverse effects were observed in 13 patients (7.4%). A third ambulatory blood pressure monitoring performed in 78 patients after a median of 15 months confirmed the persistence of the spironolactone effect. In conclusion, spironolactone administration to true resistant hypertensive patients is safe and effective in decreasing blood pressure, especially in those with abdominal obesity and lower arterial stiffness. Its addition to an antihypertensive regimen as the fourth or fifth drug is recommended.

Response: Retinal Vessel Narrowing: A Prehypertensive or Masked Hypertensive State? [Letters to the Editor]

Mon, 03 Apr 2006 13:00:13 PDT

Response: Leptin, Endothelin, NADPH Oxidase, and Heart Failure [Letters to the Editor]

Dong, F., Zhang, X., Ren, J. — Mon, 27 Mar 2006 13:01:30 PST

Acknowledgment of Reviewers [Article]

Mon, 06 Feb 2006 13:00:04 PST

Preface [Preface]

Harder, D. R. — Mon, 06 Feb 2006 12:59:37 PST

Response: ClC-Kb Mutation Revisited [Letters to the Editor]

Jeck, N., Waldegger, S., Wissinger, B., Schwab, M., Lang, F. — Mon, 30 Jan 2006 12:47:12 PST

Response: Endothelial Function and Preeclampsia [Letters to the Editor]

Khan, F., Belch, J. J.F., MacLeod, M., Mires, G. — Mon, 09 Jan 2006 12:50:02 PST

Response [Letters to the Editor]

Hu, F. — Tue, 27 Dec 2005 12:51:15 PST

Response [Letters to the Editor]

Takai, S., Miyazaki, M. — Mon, 19 Dec 2005 12:58:58 PST

Mononuclear Leukocyte Mineralocorticoid Receptors. A Possible Link Between Aldosterone and Atherosclerosis [Letters to the Editor]

Armanini, D., Fiore, C., Calo, L. A — Mon, 19 Dec 2005 12:58:47 PST

Magnesium and Arterial Stiffness [Letters to the Editor]

Kisters, K., Gremmler, B., Hausberg, M. — Mon, 05 Dec 2005 12:55:48 PST

Response [Letters to the Editor]

Laurent, S. — Mon, 05 Dec 2005 12:55:33 PST

Response [Letters to the Editor]

Mon, 14 Nov 2005 13:02:19 PST

Response [Letters to the Editor]

Grassi, D., Ferri, C., Blumberg, J. B. — Mon, 14 Nov 2005 12:59:22 PST

Response [Letters to the Editor]

Grassi, D., Desideri, G., Ferri, C., Blumberg, J. B. — Mon, 17 Oct 2005 13:02:07 PDT

Response [Letters to the Editor]

Verbeke, F., Segers, P., Verdonck, P., Vanholder, R., Van Bortel, L. M. — Mon, 17 Oct 2005 13:00:29 PDT

Response [Letters to the Editor]

Garrett, M. R., Rapp, J. P., Joe, B., Meng, H. — Mon, 10 Oct 2005 12:57:53 PDT

Response [Letters to the Editor]

Schoner, W. — Mon, 19 Sep 2005 13:57:08 PDT

Response [Letters to the Editor]

Dolan, E., Stanton, A., O'Brien, E., Staessen, J. A. — Mon, 19 Sep 2005 13:57:51 PDT

Response [Letters to the Editor]

Schoner, W. — Mon, 15 Aug 2005 13:00:36 PDT

Response [Letters to the Editor]

Fyhrquist, F., Devereux, R. B., Kjeldsen, S. E., Dahlof, B. — Mon, 18 Jul 2005 12:48:14 PDT

Inhibition of Rho-Kinase in the Nucleus Tractus Solitarius Enhances Glutamate Sensitivity in Rats [Scientific Contributions]

Tue, 05 Jul 2005 08:01:33 PDT

Abstract--The Rho/Rho-kinase pathway in the central nervous system is involved in the maintenance of dendritic spines, which form the postsynaptic contact sites of excitatory synapses. Inhibition of the Rho-kinase pathway in neuron promotes dendritic spines or branches. In contrast, activation of the Rho/Rho-kinase pathway reduces dendritic spines or branches. Recent studies suggest that morphological changes of dendritic spines occur rapidly, and spine morphology is associated with glutamate sensitivity. The aim of the present study was to determine whether Rho-kinase activity affects glutamate sensitivity in the nucleus tractus solitarii (NTS) of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). We first examined the effects of unilateral glutamate injection in the NTS. There was a significantly smaller decrease in arterial pressure in SHR than in WKY. We then examined the depressor responses evoked by unilateral glutamate injection into the NTS after preinjection of Y-27632, a specific Rho-kinase inhibitor. Preinjection of Y-27632 enhanced the glutamate response in both strains. However, the magnitude of the augmentation was significantly greater in SHR than in WKY. Furthermore, we recorded single-unit activity of NTS neurons from medulla brain slice preparations. N-methyl-D-aspartate (NMDA) or -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) was applied iontophoretically to the recorded neurons, and neuronal activity was recorded before and after Y-27632 perfusion. Y-27632 perfusion increased the response to NMDA and AMPA. These results suggest that inhibition of Rho-kinase activity in the NTS enhances glutamate sensitivity in WKY and SHR and might improve impaired glutamate sensitivity in SHR.

Response [Letters to the Editor]

Mon, 27 Jun 2005 12:48:18 PDT

Response: White Coat Hypertension, Dipping, and Nondipping in Obesity [Letters to the Editor]

Kotsis, V., Stabouli, S., Bouldin, M., Low, A., Toumanidis, S., Zakopoulos, N. — Mon, 13 Jun 2005 12:56:51 PDT

Response: Widely Possible Versus Selectively Perfect [Letters to the Editor]

de Simone, G. — Mon, 16 May 2005 13:04:54 PDT

Response [Letters to the Editor]

Townsend, S., Berkowitz, D. E. — Mon, 16 May 2005 13:04:44 PDT

Ouabain and Serum Sodium [Letters to the Editor]

Gasowski, J., Manunta, P., Bianchi, G., Staessen, J. A. — Mon, 09 May 2005 12:49:48 PDT

Response: Ouabain and Serum Sodium [Letters to the Editor]

He, F. J., MacGregor, G. A. — Mon, 09 May 2005 12:49:34 PDT

Response [Letters to the Editor]

Shibao, C., Gamboa, A., Diedrich, A., Biaggioni, I. — Mon, 25 Apr 2005 12:53:00 PDT

Response [Letters to the Editor]

Pickering, T. G. — Mon, 18 Apr 2005 12:56:42 PDT

Response: Flow-Mediated Dilation: Just a Marker of Local Shear Stress? [Letters to the Editor]

Mon, 10 Jan 2005 12:46:16 PST

Urinary Potassium Excretion and Sodium Sensitivity in Blacks (Response: Reinterpreting Sodium-Potassium Data in Salt Sensitivity Hypertension: A Prospective Debate) [Letters to the Editor]

Aviv, A., Hollenberg, N. K., Weder, A. — Mon, 03 Jan 2005 12:59:21 PST

Response [Letters to the Editor]

Gironacci, M. M. — Mon, 03 Jan 2005 12:59:00 PST

Angiotensin-(1-7) and Bradykinin in Norepinephrine Release in the Central Nervous System of Hypertension [Letters to the Editor]

Tsuda, K., Nishio, I. — Mon, 03 Jan 2005 12:58:50 PST

Response: Prognostic Significance of Serial Electrocardiographic Repolarization Changes [Letters to the Editor]

Fagard, R. H., on behalf of the Syst-Eur investigators — Mon, 06 Dec 2004 12:49:46 PST

Response [Letters to the Editor]

Schneider, M. P., Schmieder, R. E. — Mon, 06 Dec 2004 12:50:12 PST

Response: Physical Activity and Fitness in Arterial Stiffness: What Role Does Exposure Measurement Error Occupy? [Letters to the Editor]

Mon, 29 Nov 2004 12:58:10 PST

Response [Letters to the Editor]

Mon, 18 Oct 2004 13:03:10 PDT

Response [Letters to the Editor]

Jones, D. W. — Mon, 18 Oct 2004 13:02:49 PDT

Response: Is It Essential to Change the Term "Essential Hypertension" [Letters to the Editor]

Materson, B. J. — Mon, 20 Sep 2004 12:54:27 PDT

Response: Blood Pressure, Resting Energy Expenditure, and Creatine Kinase Activity: [Letters to the Editor]

Luke, A., Adeyemo, A., Kramer, H., Forrester, T., Cooper, R. S. — Mon, 26 Jul 2004 12:41:03 PDT

Response: Neural Sympathetic Activity in Essential Hypertension [Letters to the Editor]

Schlaich, M. P., Esler, M. D. — Mon, 07 Jun 2004 12:40:12 PDT

Neuroendocrine Transcriptome in Genetic Hypertension. Multiple Changes in Diverse Adrenal Physiological Systems [Scientific Contributions]

Mon, 19 Apr 2004 12:42:53 PDT

Abstract--The genetic basis of hypertension in the genetically/hereditary hypertensive (BPH/2) mouse strain is incompletely understood, although a recent genome scan uncovered evidence for several susceptibility loci. To probe the neuroendocrine transcriptome in this disease model, 12 488 probe set microarray experiments were performed on mRNA transcripts from adrenal glands of juvenile (prehypertensive) and adult BPH/2 (hypertensive), as well as the genetically/hereditary low-blood pressure (BPL/1), strains at both time points. To determine the impact of strain (BPH/2 versus BPL/1), age (juvenile versus adult), and the interaction of strain and age on gene expression levels, we performed standard 2-factor ANOVA and computed a concordance coefficient to assess the reproducibility of gene expression measurements among replicates. Of genes with significant (P<0.05) differential expression, 2647 showed strain differences, 982 showed age differences, and 757 exhibited strain-by-age interaction. Fold-changes in gene expression assayed by microarray were confirmed in a subset by real-time polymerase chain reaction (R=0.739, P=0.0094). We used a systems biology approach to evaluate alterations in contributing biochemical pathways and we statistically quantified these global pathway disturbances using the Kolmogorov-Smirnov goodness-of-fit test. We found widespread, indeed global, alterations in patterns of gene expression in diverse systems of BPH/2: in sympathochromaffin transcripts suggesting increased sympathetic stimulation; in vasoconstrictor/vasodilator systems; global reductions in carbohydrate intermediary metabolism; and increases in oxidative stress, with changes in oxygen radical forming and disposition enzymes. These analyses highlight widespread derangements in diverse physiological pathways, providing multiple avenues for further investigation into the pathogenesis of genetic hypertension.

Prevention of Cardiac Hypertrophy by Angiotensin II Type 2 Receptor Gene Transfer [Scientific Contributions]

Mon, 19 Apr 2004 12:42:24 PDT

Abstract--The role of the angiotensin II type-2 receptor (AT₂R) in cardiac hypertrophy remains elusive despite its demonstrated involvement in cardiovascular development. We have previously shown that a lentiviral vector gene delivery system is able to transduce cardiac tissue with high efficiency in vivo. Using such an approach, our objectives in the present study were 2-fold: (1) to overexpress the AT₂R in cardiac tissue after completion of natural embryonic development of the heart and (2) to determine the effects of this overexpression on cardiac hypertrophy and basal blood pressure (BP). A lentiviral vector encoding the AT₂R (lenti-AT₂R) was administered (1.5x10⁸ transducing units) into the left ventricular space of 5-day-old spontaneously hypertensive rats (SHRs). AT₂R transgene expression increased in these animals and persisted for 30 weeks. In contrast, the expression of the angiotensin II type-1 receptor remained unchanged following lenti-AT₂R treatment. At 21 weeks following gene transduction, the lenti-AT₂R-treated SHRs exhibited decreased left ventricular wall thickness compared with control animals. In contrast, basal BP did not differ between the two SHR groups. Finally, heart weight to body weight ratios indicated a significant decrease in lenti-AT₂R-treated SHRs compared with SHR controls. Our data indicate that AT₂R overexpression attenuates cardiac hypertrophy in the SHR. This beneficial outcome was observed despite the existence of elevated BP.

Response: High Blood Pressure in Acute Stroke and Subsequent Outcome: A Systematic Review [Letters to the Editor]

Willmot, M., Leonardi-Bee, J., Bath, P. M.W. — Mon, 19 Apr 2004 12:41:25 PDT

Response: Assessing the Sensitivity of Spontaneous Baroreflex Control of the Heart: Deeper Insight Into Complex Physiology [Letters to the Editor]

Taylor, J. A., Lipman, R. D. — Mon, 05 Apr 2004 12:49:17 PDT

Heme Oxygenase-1 Gene Expression Modulates Angiotensin II-Induced Increase in Blood Pressure [Scientific Contributions]

Yang, L., Quan, S., Nasjletti, A., Laniado-Schwartzman, M., Abraham, N. G. — Mon, 05 Apr 2004 12:48:33 PDT

Abstract--The heme-heme oxygenase (HO) system has been implicated in the regulation of vascular reactivity and blood pressure. This study examines the notion that overexpression of HO decreases pressor responsiveness to angiotensin II (Ang II). Five-day-old Sprague-Dawley rats received an intraleft ventricular injection of 5x10⁹ cfu/mL of retroviruses containing human HO-1 sense (LSN-HHO-1), rat HO-1 antisense (LSN-RHO-1-AS), or control retrovirus (LXSN). Three months later, rats were instrumented with femoral arterial and venous catheters for mean arterial pressure (MAP) determination and Ang II administration, respectively. Rats injected with LSN-HHO-1, but not with LXSN, expressed human HO-1 mRNA and protein in several tissues. BP increased with administration of Ang II in rats expressing and not expressing human HO-1. However, the Ang II-induced pressor response (mm Hg) in LSN-HHO-1 rats (16±3, 27±3, and 38±3 at 0.5, 2, and 10 ng) was surpassed (P<0.05) in LXSN rats (23±1, 37±2, and 52±2 at 0.5, 2, and 10 ng). Importantly, treating LSN-HHO-1 rats with the HO inhibitor tin mesoporphyrin (SnMP) enhanced (P<0.05) the Ang II-induced pressor response to a level not different from that observed in LXSN rats. Rats injected with LSN-RHO-1-AS showed a decrease in renal HO-1 protein expression and HO activity relative to control LXSN rats. Administration of Ang II (0.1 to 2 ng) caused small (4 to 5 mm Hg) but significant increases in MAP in rats injected with LSN-RHO-1-AS (P<0.05) compared with rats injected with LXSN. These data demonstrate that overexpression of HO-1 brings about a reduction in pressor responsiveness to Ang II, which is most likely due to increased generation of an HO-1 product, presumably CO, with the ability to inhibit vascular reactivity to constrictor stimuli.

Gene Therapy and Heme Oxygenase Coming of Age [Editorial Commentary]

Roman, R. J. — Mon, 05 Apr 2004 12:47:55 PDT

Statins Augment Collateral Growth in Response to Ischemia But They Do Not Promote Cancer and Atherosclerosis [Scientific Contributions]

Mon, 05 Apr 2004 12:47:23 PDT

Abstract--3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, or statins, are widely prescribed to lower cholesterol. Recent reports suggest that statins may promote angiogenesis in ischemic tissues. It remains to be elucidated whether statins potentially enhance unfavorable angiogenesis associated with tumor and atherosclerosis. Here, we induced hind limb ischemia in wild-type mice by resecting the right femoral artery and subsequently inoculated cancer cells in the same animal. Cerivastatin enhanced blood flow recovery in the ischemic hind limb as determined by laser Doppler imaging, whereas tumor growth was significantly retarded. Cerivastatin did not affect capillary density in tumors. Cerivastatin, pitavastatin, and fluvastatin inhibited atherosclerotic lesion progression in apolipoprotein E-deficient mice, whereas they augmented blood flow recovery and capillary formation in ischemic hind limb. Low-dose statins were more effective than high-dose statins in both augmentation of collateral flow recovery and inhibition of atherosclerosis. These results suggest that statins may not promote the development of cancer and atherosclerosis at the doses that augment collateral flow growth in ischemic tissues.

Statin Therapy: Having the Good Without the Bad [Editorial Commentary]

Liao, J. K. — Mon, 29 Mar 2004 13:01:51 PST

Response [Letters to the Editor]

Chobanian, A. V., Roccella, E. J. — Mon, 22 Mar 2004 12:43:04 PST

Response: Rapid Nongenomic Effects of Aldosterone on Human Forearm Vasculature [Letters to the Editor]

Schmidt, B. M.W., Schmieder, R. E. — Mon, 23 Feb 2004 13:05:15 PST

Response: Does Hypomagnesemia Have an Adaptive Role in Hypertension? [Letters to the Editor]

Northcott, C. A., Watts, S. W. — Mon, 23 Feb 2004 13:03:05 PST

Response [Letters to the Editor]

Chobanian, A. V., Roccella, E. J. — Mon, 23 Feb 2004 13:02:09 PST

Response [Letters to the Editor]

Chobanian, A. V., Roccella, E. J. — Mon, 23 Feb 2004 13:01:42 PST

Response: Gold Standards for Baroreflex Gain [Letters to the Editor]

Lipman, R. D., Taylor, J. A. — Mon, 23 Feb 2004 12:57:51 PST

Response: Terminology for Describing the Elastic Behavior of Arteries [Letters to the Editor]

Budge, M. M., Gosling, R. G. — Mon, 23 Feb 2004 12:57:26 PST

Response [Letters to the Editor]

Mon, 16 Feb 2004 12:30:38 PST

Response: Aspirin Administered at Bedtime as Opposed to Upon Wakening Has an Effect on Ambulatory Blood Pressure: Further Evidence [Letters to the Editor]

Mon, 16 Feb 2004 12:30:11 PST

Response: Insulin-Leptin Interplay May Differ Among Tissues: [Letters to the Editor]

Vecchione, C., Lembo, G. — Mon, 09 Feb 2004 12:44:34 PST

Response: Adiponectin Concentrations in Preeclampsia [Letters to the Editor]

Sattar, N., Ramsey, J., Jamieson, N., Greer, I. A. — Mon, 02 Feb 2004 12:54:44 PST

Response: Is Low-Heat Shock Protein 70 a Primary or a Secondary Event in the Development of Atherosclerosis? [Letters to the Editor]

Pockley, A. G., Georgiades, A., Thulin, T., de Faire, U., Frostegard, J. — Mon, 02 Feb 2004 12:53:44 PST

Response [Letters to the Editor]

Mon, 26 Jan 2004 12:41:27 PST

Response [Letters to the Editor]

Egan, B. M. — Mon, 19 Jan 2004 13:16:29 PST

Guidelines for Hypertension: Are Quality-Assurance Measures on Target? [Scientific Contributions]

Singer, G. M., Izhar, M., Black, H. R. — Mon, 19 Jan 2004 13:14:50 PST

Abstract--Guideline committees recommend targets of treatment based on trial data on efficacy and effectiveness. Quality-assurance initiatives apply these parameters in the general practice setting. Therefore, targets must be feasible and achievable by the practicing physicians who are judged by these targets as goals for care. We evaluated 437 patients in the Rush University Hypertension Clinic using the Health Employer Data Information Set (HEDIS) measures for 2000 to assess goal achievement in a practice-based setting. We compared guideline achievement of uncomplicated hypertensive and diabetic subjects to standards dictated by HEDIS, the 6th Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI), and the American Diabetic Association (ADA)/National Kidney Foundation (NKF). Overall, 276 (63%) patients achieved SBP goal, with 376 (86%) achieving DBP goal and 358 (59%) achieving both goals. However, in the 20% of patients who were diabetic, only 52% had a BP of <140 mm Hg and <90 mm Hg, whereas only 22% achieved the more stringent goals of JNC VI of <130 mm Hg systolic and <85 mm Hg diastolic and only 15% achieved the ADA/NKF goals of <130 mm Hg systolic and <80 mm Hg diastolic. Although goal was achievable in most uncomplicated hypertension, hypertension in diabetes was more difficult to control, despite being more likely to receive enhanced benefit from effective management. Goal-oriented strategy, especially in diabetic subjects, should be aggressively sought rather than relaxing goals to promote achievement.

Acromegalic Patients Show the Presence of Hypertrophic Remodeling of Subcutaneous Small Resistance Arteries [Scientific Contributions]

Mon, 19 Jan 2004 13:14:17 PST

Abstract--Structural alterations of small resistance arteries in patients with essential hypertension (EH) are mostly characterized by inward eutrophic remodeling. However, we have observed the presence of hypertrophic remodeling in patients with renovascular hypertension, as well as in patients with noninsulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure. Growth hormone may stimulate in vitro proliferation of vascular smooth muscle cells. However, no data are presently available about small artery structure in acromegalic patients. Therefore, we have investigated the structure of subcutaneous small arteries in 12 normotensive (NT) subjects, in 12 EH subjects, and in 9 acromegalic patients (APs). All subjects underwent biopsy of the subcutaneous fat; then, small resistance arteries were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media-to-lumen ratio, the media cross-sectional area together with remodeling, and growth indices were calculated. Demographic variables were similar in the three groups, except for blood pressure. The media-to-lumen ratio was significantly greater in EH and AP, compared with NT. No difference was observed between EH and AP. The media cross-sectional area was significantly greater in AP compared with EH and with NT. The calculation of remodeling and growth index suggests the presence of eutrophic remodeling in EH (growth index 0%) and of hypertrophic remodeling in AP (growth index 40%). In conclusion, our data suggest the presence of hypertrophic remodeling of subcutaneous small resistance arteries of AP, probably as a consequence of growth-stimulator properties of IGF-1.

Response: Vitamin C in Heart Failure: Hope! [Letters to the Editor]

Mon, 19 Jan 2004 13:05:34 PST

Aldosterone Antagonism and Arterial Stiffness [Letters to the Editor]

White, W. B., Duprez, D. — Mon, 12 Jan 2004 12:54:08 PST

Response [Letters to the Editor]

Redon, J., Tormos, M. C., Chaves, F. J., Espinosa, O., Iradi, A., Saez, G. T. — Mon, 12 Jan 2004 12:50:46 PST

Response: Augmentation Index and the Radial-to-Aortic Transfer Function [Letters to the Editor]

Millasseau, Ritter, Chowienczyk — Mon, 22 Sep 2003 12:53:53 PDT

Response: Hypotension and Reduced Catecholamines in Neuropeptide Y Transgenic Rats [Letters to the Editor]

Michalkiewicz, Knestaut, Bytchkova, Michalkiewicz — Mon, 22 Sep 2003 12:50:57 PDT

Response [Letters to the Editor]

Taddei, Virdis, Ghiadoni, Versari, Salvetti, Magagna, Salvetti — Tue, 02 Sep 2003 12:39:16 PDT

Acknowledgment to Reviewers [Acknowledgment to Reviewers]

Mon, 18 Aug 2003 12:38:55 PDT

Response [Letters to the Editor]

Palmer, Mancia — Mon, 18 Aug 2003 12:34:14 PDT

Response: Aortic Augmentation Index and Radial-to-Aortic Transfer Function [Letters to the Editor]

Millasseau, Ritter, Chowienczyk — Mon, 04 Aug 2003 12:52:46 PDT

Response: Hypertension and Low-Level Lead Exposure in African Americans: A Public Health Reality [Letters to the Editor]

Vupputuri, Batuman, He — Mon, 28 Jul 2003 12:59:28 PDT

Correction [Correction]

Mon, 07 Jul 2003 12:44:59 PDT

Correction [Correction]

Mon, 30 Jun 2003 12:48:24 PDT

Response: Does the Bradykinin B2 Receptor Function as a Protease-Activated Receptor? [Letters to the Editor]

Marceau, Houle, Molinaro, Adam — Mon, 30 Jun 2003 12:47:10 PDT

Response [Letters to the Editor]

Morris, Lin, Wang — Mon, 23 Jun 2003 12:49:02 PDT

News From the American Heart Association [News From the American Heart Association]

Mon, 02 Jun 2003 12:50:01 PDT

Meetings Calendar [Meetings Calendar]

Mon, 02 Jun 2003 12:49:40 PDT

Response [Letters to the Editor]

Lantelme, Mestre, Milon — Mon, 21 Apr 2003 13:00:17 PDT

Response: What Is Old Is Not Always Best [Letters to the Editor]

Myerson, Pennell — Mon, 21 Apr 2003 12:59:51 PDT

Response: Multifactorial Disease: Glu298asp of Endothelial Nitric Oxide Synthase [Letters to the Editor]

Noiri, Fujita, Tokunaga — Mon, 14 Apr 2003 12:49:58 PDT

Response: Pulse Wave Velocity, Heart Rate, and Blood Pressure [Letters to the Editor]

Lantelme, Mestre, Gressard, Milon, Lievre — Mon, 28 Oct 2002 12:36:43 PST

Response: Heart Rate and Pulse Wave Velocity [Letters to the Editor]

Lantelme, Mestre, Lievre, Gressard, Milon — Mon, 21 Oct 2002 12:57:38 PDT

Response: Endothelin Antagonism and Insulin's Vascular Effects [Letters to the Editor]

Miller, Busija — Mon, 21 Oct 2002 12:55:51 PDT

Response: How to Measure Blood Pressure Variability [Letters to the Editor]

Mancia, Sega — Mon, 16 Sep 2002 12:53:42 PDT

Response [Letters to the Editor]

Zhuo, Mendelsohn, Ohishi — Mon, 09 Sep 2002 12:40:03 PDT