Published online before print January 8, 2007, doi: 10.1161/01.HYP.0000255983.32896.b9
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2007;49:535.)
© 2007 American Heart Association, Inc.
Original Articles |
Excessive Sympathetic Activation in Heart Failure With Obesity and Metabolic Syndrome
Characteristics and Mechanisms
From the Clinica Medica, Dipartimento di Medicina Clinica (G.G., F.Q.-T., F.S., R.D., G.M.), Prevenzione e Biotecnologie Sanitarie, Università Milano-Bicocca, Ospedale San Gerardo, Milan, Italy; Istituto Auxologico Italiano (G.G., G.S., G.M.), Milan, Italy; and Centro Interuniversitario di Fisiologia Clinica e Ipertensione (G.G., G.B., G.M.), Milan, Italy.
Correspondence to Guido Grassi, Clinica Medica, Ospedale San Gerardo dei Tintori, Via Pergolesi 33, 20052 Milan, Italy. E-mail guido.grassi{at}unimib.it
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Congestive heart failure is characterized by sympathetic activation, which has also been described in the metabolic syndrome. No information exists, however, as to whether the sympathostimulating effects of these 2 conditions summate when heart failure is complicated by the metabolic syndrome, leading to an exceedingly high adrenergic drive. This is clinically relevant, because in heart failure sympathetic activation is closely related to mortality. We studied 48 control subjects (age: 58.4±1.6 years, mean±SEM) and 89 age-matched heart failure patients (New York Heart Association class II), of whom 47 were without and 42 were with metabolic syndrome. Measurements included blood pressure (Finapres), heart rate (ECG), and sympathetic nerve traffic (microneurography) at rest and during baroreceptor manipulation. Waist circumference, blood pressure, and metabolic variables were greater in heart failure with metabolic syndrome than in heart failure without metabolic syndrome and in control subjects. Left ventricular ejection fraction and end-diastolic diameter were similarly altered in the 2 heart failure groups. Compared with control subjects, sympathetic nerve activity was greater in heart failure patients without metabolic syndrome (64.7±3.2 versus 45.8±2.9 bursts/100 heartbeats; P<0.01), a further pronounced increase being detected in those with metabolic syndrome (80.9±3.2 bursts/100 heartbeats; P<0.01). In the multivariate analysis, waist circumference and body mass index were the variables most closely related to sympathetic activation. Compared with control subjects, baroreflex responses were significantly attenuated in the 2 heart failure groups, the impairment being more marked in the group with than without metabolic syndrome. Thus, obesity and metabolic syndrome potentiate the sympathetic activation characterizing heart failure. This potentiation is likely to mainly depend on metabolic and baroreflex mechanisms.
Key Words: baroreflex • metabolic syndrome • heart failure • sympathetic nervous system
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Indirect and direct indices of sympathetic activity, such as venous plasma norepinephrine, plasma norepinephrine spillover from adrenergic nerve terminals, and muscle sympathetic nerve firing rate, have shown that sympathetic cardiovascular influences are increased in a high-risk condition such as congestive heart failure (CHF).1–4 They have also shown that this neuroadrenergic alteration is directly related to the severity of the CHF state1,4 and similar in magnitude in CHF of ischemic or idiopathic dilated etiology.1,5 Evidence has also been provided that a hyperadrenergic state characterizes the clustering of risk factors known as metabolic syndrome (MS),6–8 which also represents a high-risk condition for the development of CHF.9 Several studies have shown that some components of MS (eg, obesity and hypertension) have sympathostimulating effects,10–13 which can, to some extent, also be seen in CHF patients.14 Whether and to what extent the clustering of blood pressure, body weight, and metabolic alterations known as MS leads to a further increase in sympathetic drive is unknown, however. This is a question of clinical relevance, because CHF and MS frequently coexist in the same patient15,16 and, in CHF, the degree of sympathetic activation is related to patient’s mortality.17,18
The present study has been undertaken to determine the impact of CHF complicated by MS on sympathetic function, as assessed by either microneurographic nerve traffic recording or venous plasma norepinephrine assay. The study was also aimed at assessing whether and to what extent reflex mechanisms are involved in the sympathetic overactivity possibly occurring in CHF combined with MS. This was done by examining in the study population baroreceptor influences on sinus node activity, as well as on muscle sympathetic nerve traffic.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Study Population
The study population consisted of 137 subjects of both genders (85 men and 52 women, with age ranging from 49 to 66 years). Eighty-nine subjects had a CHF, whereas the remaining subjects were age-matched healthy controls. Subjects with CHF were recruited if belonging to New York Heart Association class II, with only a modest reduction in echocardiographic ejection fraction (35% to 45%) and with or without the concomitant presence of MS, as defined at a routine control visit a few days before the study. MS was diagnosed based on the presence of
3 of the 5 diagnostic criteria proposed by the National Cholesterol Educational Program Adult Treatment Panel in the 2005 revised version,19 that is, abdominal obesity (waist circumference >102 cm in men and >88 cm in women), fasting hypertriglyceridemia (plasma triglycerides 150 mg/dL), low high-density lipoprotein cholesterol (plasma high-density lipoprotein cholesterol <40 mg/dL in men and <50 mg/dL in women), a blood pressure elevation (blood pressure values 130/85 mm Hg or treatment with antihypertensive drugs), and fasting hyperglycemia (plasma glucose >100 mg/dL).19 Subjects were excluded from the study if they had secondary hypertension, atrial fibrillation or other major cardiac arrhythmias, history of myocardial infarction in the 12 months preceding the study, clinical or laboratory evidence of valvular heart disease, history of smoking and/or excessive alcohol consumption, presence of renal insufficiency or other conditions known to affect autonomic cardiovascular control, history of regular exercise habit or involvement in physical training programs, and history of symptoms suggestive of obstructive sleep apnea syndrome. Each subject underwent sphygmomanometric blood pressure measurements, as well as assessment of body weight, body mass index, and waist circumference. Total serum cholesterol, plasma triglycerides, high-density lipoprotein plasma cholesterol (enzymatic method), and glucose (standard glucose oxidase method) were measured in the fasting state from a venous blood sample. Subjects were classified as one of the following: (1) healthy control subjects (n=48), (2) patients with CHF (n=47) of either ischemic (n=30) or idiopathic (n=17) nature without MS, or (3) patients with congestive CHF (n=42) of either ischemic (n=26) or idiopathic (n=16) nature who met the definition of MS. Control subjects were under no drug treatment, and they were studied on an outpatient basis. No patient with CHF was under antidiabetic drugs. All of the CHF patients were under treatment with furosemide, angiotensin-converting enzyme inhibitors, ß-blockers, or angiotensin II receptor blockers. With the exception of loop diuretics, cardiovascular drugs were withdrawn 4 to 6 days before the study, which was performed after a 2- to 3-day hospitalization. The study protocol was approved by the ethics committee of 1 of the institutions involved. All of the subjects gave written consent to participate at the study after being informed of its nature and purpose.
Measurements
The details of the procedures used to assess sphygmomanometric and beat-to-beat (Finapres 2300, Ohmeda) systolic (S) and diastolic (D) blood pressure (BP) values, heart rate ([HR] ECG), respiration rate (pneumotachograph), echocardiographic variables (left ventricular end-diastolic diameter and left ventricular ejection fraction), multiunit recording of efferent muscle sympathetic nerve activity ([MSNA] microneurography), plasma norepinephrine (high-performance liquid chromatography), and plasma renin activity (radioimmunoassay) have been described previously.4,5,7,11,14,20–22 Mean BP was calculated by adding one third of pulse pressure to diastolic BP. Beat-to-beat BP, HR, respiration rate, and MSNA were displayed on a thermic paper of an ink polygraph (Gould 3800). Under baseline conditions, MSNA was quantified either as number of bursts per minute or as number of bursts per 100 heart beats. Either quantification has been shown to be highly reproducible, that is, to differ by only 3.8% when assessed on the same tracing on 2 separate occasions by a single investigator.23 Baroreceptor modulation of MSNA and HR was assessed by the vasoactive drug technique.4,5,7,11,14 Briefly, phenylephrine was incrementally infused in an antecubital vein at doses of 0.3, 0.6, and 0.9 µg/kg per minute, each step being maintained for 5 minutes. Nitroprusside was also incrementally infused in an antecubital vein at doses of 0.4, 0.8, and 1.2 µg/kg per minute, each step being maintained for 5 minutes. In all of the subjects, the drug initially infused was selected randomly, and the end of the first infusion was separated from the beginning of the second one by a suitable recovery period. Systolic BP, diastolic BP, mean BP, MSNA, and HR were averaged for the 5 minutes before infusion and for the 5 minutes of each step infusion. Baroreceptor modulation of MSNA and HR was estimated by calculating the absolute and percentage changes in integrated activity (ie, mean burst amplitude multiplied by bursts number over time) and the changes in HR in relation to the BP changes induced by each dose of phenylephrine and nitroprusside. In each patient, the ratio between MSNA and HR changes was analyzed separately for the 3-step infusions of phenylephrine and nitroprusside. The data were then further averaged to obtain MSNA- or HR-baroreflex sensitivity.
Protocol and Data Analysis
All of the subjects were brought to the laboratory in the morning after an overnight fasting. They were put in the supine position and fitted with intravenous cannulas, microelectrodes for MSNA recording, and other measuring devices. Blood samples for norepinephrine and renin assay were then taken, and BP was measured 3 times with a mercury sphygmomanometer. After a 30-minute interval, BP, HR, respiration rate, and MSNA were continuously measured during an initial 10-minute basal state, the intravenous infusion of 1 vasoactive drug, a 45-minute recovery period followed by a second 10-minute basal state, and the intravenous infusion of the second vasoactive drug.
Data were collected in a quiet room at a constant temperature of 20°C to 21°C and analyzed by a single investigator unaware of the belonging of the patients to different groups. Baseline individual values were averaged for each group and expressed as mean±SEM. This procedure was also followed for the changes in mean BP, MSNA, and HR induced by each dose of vasoactive drugs. Comparisons between data obtained in different groups were made by 2-way ANOVA. The 2-tailed t test for unpaired observations was used to locate between-group differences. The Bonferroni correction was used to account for multiple comparisons. A multivariate analysis was also performed with age, gender, BP, left ventricular ejection fraction, body mass index, waist circumference, plasma triglycerides, blood glucose, and high-density lipoprotein cholesterol as independent variables and MSNA as the dependent one. A value of P<0.05 was considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Baseline Values
As shown in the Table, CHF patients with MS, CHF patients without MS, and control subjects were matched for age. Compared with control subjects, patients with CHF displayed a significant reduction in left ventricular ejection fraction, as well as a significant increase in left ventricular end-diastolic diameter, HR, plasma renin activity, and plasma norepinephrine. The average values were superimposable in the groups without and with MS, which also showed similar ranges of left ventricular ejection fraction and end-diastolic diameter. As expected, sphygmomanometric and finger BPs, body mass index, waist circumference, and biochemical variables related to glucose and lipid metabolism were all altered in CHF patients with MS when compared both with control subjects and CHF patients without MS (Table).
|
Sympathetic Activity
The individual and the average MSNA data for the 3 groups are shown in Figure 1. MSNA showed an interindividual variability within each group. Compared with control subjects, CHF patients without MS displayed greater MSNA values (+41.2%), which showed, however, a further increase (+38.4%) in CHF patients with MS. The between-group average differences were statistically significant, and the results were similar both when MSNA was quantified as burst incidence per unit of time and as burst incidence corrected for HR. This was the case also when we excluded from the analysis individuals in which sphygmomanometric BP was 130 mm Hg systolic and/or >85 mm Hg diastolic, that is, when MS included the BP elevation as a component (Figure 2). In the multivariate analysis performed on the whole study sample, MSNA was directly related to waist circumference and body mass index (ß-coefficient 0.64±0.08 and 0.60±0.09, respectively; P<0.01 for both) while showing no significant relationship with other hemodynamic and metabolic variables.
|
|
Baroreflex Responses
Figure 3 (top) shows that, in control subjects and in CHF patients, HR and MSNA decreased linearly as mean BP increased progressively from the lowest value observed with the greatest nitroprusside dose to the highest value observed with the greatest phenylephrine dose, the overall range of HR and MSNA changes being markedly less than that observed in controls. Figure 3 (top) also shows that, in CHF patients, because of their higher baseline MSNA and HR values, the set point of the baroreflex was displaced to the right and more so when MS was present. Furthermore, as shown in the bottom of Figure 3, the sensitivity of baroreceptor HR and baroreceptor MSNA was markedly reduced in CHF patients without MS as compared with control subjects, a further significant reduction occurring in patients in which CHF was combined with MS. This is shown also in Figure 4, which illustrates the HR and MSNA changes in response to stepwise doses of phenylephrine and nitroprusside. Baseline MSNA was significantly and inversely related to MSNA-baroreflex sensitivity in all of the study’s sample (r=–0.38; P<0.01). No such correlation was found between baseline HR values and HR baroreflex sensitivity (r=–0.08; P value not significant).
|
HR) or MSNA (
|
, —) and in CHF patients without ( |
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Our data provide evidence that CHF associated with obesity and MS considerably enhances the already elevated levels of MSNA typical of this condition. This confirms the results of previous studies that, in the absence of any concomitant disease, MS is associated with sympathetic activation.6–8 It documents for the first time, however, that this sympathostimulating influence is retained even under conditions in which sympathetic activity is already elevated.
Our study also provides information on the mechanisms that may be responsible for the greater sympathetic activation characterizing a CHF state complicated by MS. We can rule out that the greater sympathetic activity seen when CHF was associated with MS was because of a greater CHF severity, because patients were selected only if their CHF belonged to New York Heart Association class II and the groups with or without MS had similar average values (as well as similar ranges) of left ventricular ejection fraction and end-diastolic diameter. Furthermore, they had similar plasma renin activity values, suggesting a similar degree of renin-angiotensin system activation. We can also rule out that differences in drug treatment were responsible, because hospitalization allowed drugs used in CHF (and known to affect sympathetic cardiovascular influences24–27) to be withdrawn and to uniformly maintain all of the patients under diuretic treatment only. We can finally rule out that a between-group imbalance of patients with ischemic CHF versus idiopathic cardiomyopathy was involved, because for the same severity these 2 conditions have been shown to be similarly capable of triggering a sympathetic activation.5 This means that the greater sympathetic activation should be ascribed to the components of this condition. In this context, although a BP elevation has been shown to exert sympathostimulating effects,10–11,14 we can rule out that the BP component played a major role, because, in CHF patients with MS, MSNA was greater than in those without MS also when hypertensive subjects were excluded, and, in the multivariate analysis, no significant independent relationship was found between BP and MSNA. We can, on the other hand, suggest that the increase in body weight plays an important role, because, in the multivariate analysis, body mass index did show an independent relationship with MSNA. It is interesting to note that in this analysis MSNA was independently related also to waist circumference, suggesting an independent sympathostimulating effect of visceral adiposity. We can speculate that substances with sympathostimulating effects of which the circulating plasma levels are increased in obesity (leptin, adiponectin, etc28,29) are responsible for the finding. It is also possible that factors such as insulin and sleep apnea play an important role, because insulin is a powerful stimulant of MSNA29 and its plasma levels are already elevated in CHF because of an insulin resistance state,30 and, even in absence of a clinical history, sleep apnea might have been present and promoted a sympathetic activation via chemoreceptor activation and possibly sleep deprivation.31,32 In this context, however, it should be emphasized that, compared with CHF patients without MS, in our CHF patients with MS the set point of the baroreflex was displayed to the right in relation to the greater baseline HR and MSNA. Furthermore, the baroreflex ability to modulate MSNA was more markedly impaired in these patients. This means that the ability of the baroreflex to tonically and phasically restrain MSNA is more markedly impaired in CHF with than without MS. Our study, thus, indicates baroreflex derangement as a further mechanism behind the excessive sympathetic activation seen when CHF and MS are combined together.
Several other findings deserve to be discussed. First, plasma norepinephrine, although significantly greater in CHF than in control subjects, did not differ in patients with or without MS. This represents a further example that, in humans, plasma levels of the adrenergic neurotransmitter often represent a less than optimal marker of changes in sympathetic drive presumably because short- and long-term reproducibility of plasma norepinephrine assay is limited,23 and plasma norepinephrine levels depend not only on secretion but also on tissue clearance and reuptake.33,34 Second, our data do not clarify whether the excessive sympathetic activation occurring in CHF complicated by MS is limited to the muscle vascular district or whether it is generalized to the whole cardiovascular system. Evidence is available, however, that in both congestive CHF and MS, sympathetic outflow is increased not only at the level of the skeletal muscle but also in the coronary and renal circulation,2,8 suggesting that a generalized extrapotentiation of sympathetic activity by MS in CHF is a likely possibility. Third, in CHF, adrenergic activity is closely related to cardiovascular mortality.17,18 Thus, the present demonstration of a greater sympathoactivation by MS in CHF may offer information of prognostic significance and help proper assessment of the overall risk in a number of patients.
Perspectives
The results of the present study demonstrate that MS potentiates the sympathetic activation characterizing mild CHF. They further show that the most important determinant of this activation is likely to be visceral obesity with a contribution, however, from a greater baroreflex dysfunction compared with that already characterizing heart failure. Future studies are needed to determine whether and to what extent the above-mentioned alterations can be reversed by the therapeutic intervention.
|
Acknowledgments |
|---|
Source of Funding
This work has been in part supported by a research grant from the Italian Society of Hypertension.
Disclosures
None.
Received September 27, 2006; first decision October 12, 2006; accepted December 10, 2006.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
- Francis GS, Benedict C, Johnstone DE, Kirlin PC, Nicklas J, Liang CS, Kubo SH, Rudin-Toretsky E, Yusuf S for the SOLVD Investigators. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure: a substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation. 1990; 82: 1724–1729.
[Abstract/Free Full Text] - Hasking GJ, Esler MD, Jennings LL, Burton D, Johns JA, Korner PI. Norepinephrine spillover to plasma in heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation. 1986; 73: 615–621.
[Abstract/Free Full Text] - Leimbach WN, Wallin BG, Victor RG, Aylward PE, Sundlof G, Mark AL. Direct evidence from intraneural recordings for increased central sympathetic outflow in patients with heart failure. Circulation. 1986; 73: 913–919.
[Abstract/Free Full Text] - Grassi G, Seravalle G, Cattaneo BM, Lanfranchi A, Vailati S, Giannattasio C, Del Bo A, Sala C, Bolla GB, Pozzi M. Sympathetic activation and loss of reflex sympathetic control in mild congestive heart failure. Circulation. 1995; 92: 3206–3211.
[Abstract/Free Full Text] - Grassi G, Seravalle G, Bertinieri G, Turri C, Stella ML, Scopelliti F, Mancia G. Sympathetic and reflex abnormalities in heart failure secondary to ischaemic or idiopathic dilated cardiomyopathy. Clin Sci (Lond). 2001; 101: 141–146.[Medline] [Order article via Infotrieve]
- Huggett RJ, Burns J, Mackintosh AF, Mary DA. Sympathetic neural activation in nondiabetic metabolic syndrome and its further augmentation by hypertension. Hypertension. 2004; 44: 847–852.
[Abstract/Free Full Text] - Grassi G, Dell’Oro R, Quarti-Trevano F, Scopelliti F, Seravalle G, Paleari F, Gamba PL, Mancia G. Neuroadrenergic and reflex abnormalities in patients with metabolic syndrome. Diabetologia. 2005; 48: 1359–1365.[CrossRef][Medline] [Order article via Infotrieve]
- Straznicky NE, Lambert EA, Lambert GW, Masuo K, Esler MD, Nestel PJ. Effects of dietary weight loss on sympathetic activity and cardiac risk factors associated with the metabolic syndrome. J Clin Endocrinol Metab. 2005; 90: 5998–6005.
[Abstract/Free Full Text] - Ingelsson E, Arnlov J, Lind L, Sundstrom J. The metabolic syndrome and risk for heart failure in middle-aged men. Heart. 2006; 92: 1409–1413.
[Abstract/Free Full Text] - Anderson EA, Sinkey CA, Lawton WJ, Mark AL. Elevated sympathetic nerve activity in borderline hypertensive humans. Evidence from direct intraneural recordings. Hypertension. 1989; 14: 177–183.
[Abstract/Free Full Text] - Grassi G, Cattaneo BM, Seravalle G, Lanfranchi A, Mancia G. Baroreflex control of sympathetic nerve activity in essential and secondary hypertension. Hypertension. 1998; 31: 68–72.
[Abstract/Free Full Text] - Grassi G, Seravalle G, Cattaneo BM, Bolla GB, Lanfranchi A, Colombo M, Giannattasio C, Brunani A, Cavagnini F, Mancia G. Sympathetic activation in obese normotensive subjects. Hypertension. 1995; 25: 560–563.
[Abstract/Free Full Text] - Grassi G, Dell’Oro R, Facchini A, Quarti Trevano F, Bolla GB, Mancia G. Effect of central and peripheral body fat distribution on sympathetic and baroreflex function in obese normotensives. J Hypertens. 2004; 22: 2363–2369.[CrossRef][Medline] [Order article via Infotrieve]
- Grassi G, Seravalle G, Quarti Trevano F, Dell’Oro R, Bolla GB, Mancia G. Effects of hypertension and obesity on the sympathetic activation of heart failure patients. Hypertension. 2003; 42: 873–877.
[Abstract/Free Full Text] - Kip KE, Marroquin OC, Kelley DE, Johnson BD, Kelsey SF, Shaw LJ, Rogers WJ, Reis SE. Clinical importance of obesity versus the metabolic syndrome in cardiovascular risk in women: a report from the Women’s Ischemia Syndrome Evaluation (WISE) study. Circulation. 2004; 109: 706–713.
[Abstract/Free Full Text] - Zeller M, Steg PG, Ravisy J, Laurent Y, Janin-Manificat L, L’Huillier I, Beer JC, Oudot A, Rioufol G, Makki H, Farnier M, Rochette L, Verges B, Cottin Y, for the Observatoire des Infarctus de Cote-d’Or Survey Working Group. Prevalence and impact of metabolic syndrome on hospital outcomes in acute myocardial infarction. Arch Intern Med. 2005; 165: 1192–1198.
[Abstract/Free Full Text] - Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984; 311: 819–823.[Abstract]
- Swedberg K, Eneroth P, Kjekshus J, Wilhelmsen L, for the Consensus Trial Study Group. Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. Circulation. 1990; 82: 1730–1736.
[Abstract/Free Full Text] - Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005; 112: 2735–2752.
[Free Full Text] - Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I. Recommendations for quantitation of left ventricle by two dimensional echocardiography. J Am Soc Echocardiogr. 1989; 2: 358–367.[Medline] [Order article via Infotrieve]
- Hjemdahl P, Daleskog M, Kahan T. Determination of plasma catecholamines by high performance liquid chromatography with electrochemical detection: comparison with a radioenzymatic method. Life Sci. 1979; 25: 131–138.[CrossRef][Medline] [Order article via Infotrieve]
- Sealey JE, Laragh JH. How to do a plasma renin assay. Cardiovasc Med. 1977; 2: 1079–1092.
- Grassi G, Bolla GB, Seravalle G, Turri C, Lanfranchi A, Mancia G. Comparison between reproducibility and sensitivity of muscle sympathetic nerve traffic and plasma noradrenaline in man. Clin Sci (Lond). 1997; 92: 285–289.[Medline] [Order article via Infotrieve]
- Grassi G, Cattaneo BM, Seravalle G, Lanfranchi A, Pozzi M, Morganti A, Carugo S, Mancia G. Effects of chronic ACE inhibition on sympathetic nerve traffic and baroreflex control of circulation in heart failure. Circulation. 1997; 96: 1173–1179.
[Abstract/Free Full Text] - Grassi G, Spaziani D, Seravalle G, Bertinieri G, Dell’Oro R, Cuspidi C, Mancia G. Effects of amlodipine on sympathetic nerve traffic and baroreflex control of circulation in heart failure. Hypertension. 1999; 33: 671–675.
[Abstract/Free Full Text] - Azevedo ER, Kubo T, Mak S, Al-Hesayen A, Schofield A, Allan R, Kelly S, Newton GE, Floras JS, Parker JD. Nonselective versus selective beta-adrenergic receptor blockade in congestive heart failure: differential effects on sympathetic activity. Circulation. 2001; 104: 2194–2199.
[Abstract/Free Full Text] - Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, Kurabayashi M. Effects of candesartan on cardiac sympathetic nerve activity in patients with congestive heart failure and preserved left ventricular ejection fraction. J Am Coll Cardiol. 2005; 45: 661–667.
[Abstract/Free Full Text] - Grassi G. Leptin, sympathetic nervous system, and baroreflex function. Curr Hypertens Rep. 2004; 6: 236–240.[Medline] [Order article via Infotrieve]
- Esler M, Straznicky N, Eikelis N, Masuo K, Lambert G, Lambert E. Mechanisms of sympathetic activation in obesity-related hypertension. Hypertension. 2006; 48: 787–796.
[Free Full Text] - Ingelsson E, Sundstrom J, Arnlov J, Zethelius B, Lind L. Insulin resistance and risk of congestive heart failure. JAMA. 2005; 294: 334–341.
[Abstract/Free Full Text] - Narkiewicz K, van de Borne PJ, Cooley RL, Dyken ME, Somers VK. Sympathetic activity in obese subjects with and without obstructive sleep apnea. Circulation. 1998; 98: 772–776.
[Abstract/Free Full Text] - Gangwisch JE, Heymsfield SB, Boden-Albala B, Buijs RM, Kreier F, Pickering TG, Rundle AG, Zammit GK, Malaspina D. Short sleep duration as a risk factor for hypertension: analyses of the first National Health and Nutrition Examination Survey. Hypertension. 2006; 47: 833–839.
[Abstract/Free Full Text] - Grassi G, Esler M. How to assess sympathetic activity in humans. J Hypertens. 1999; 17: 719–734.[CrossRef][Medline] [Order article via Infotrieve]
- Folkow B, Di Bona GF, Hjemdahl P, Toren PH, Wallin BG. Measurements of plasma norepinephrine concentrations in human primary hypertension. A word of caution on their applicability for assessing neurogenic contributions. Hypertension. 1983; 5: 399–403.
[Abstract/Free Full Text]
This article has been cited by other articles:
 |
|
 |
|
  Y. B. Sverrisdottir, T. Mogren, J. Kataoka, P. O. Janson, and E. Stener-Victorin Is polycystic ovary syndrome associated with high sympathetic nerve activity and size at birth? Am J Physiol Endocrinol Metab, March 1, 2008; 294(3): E576 - E581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. F. Drager, E. M. Krieger, and G. Lorenzi-Filho Sympathetic Activity, Heart Failure, Obesity, and Metabolic Syndrome: Is There Any Role for Obstructive Sleep Apnea? Hypertension, June 1, 2007; 49(6): e38 - e38. [Full Text] [PDF]
|
|
|
|
|
|
G. Grassi, G. Seravalle, F. Q. Trevano, F. Scopelliti, R. Dell'Oro, G. Bolla, and G. Mancia Response to Sympathetic Activity, Heart Failure, Obesity, and Metabolic Syndrome: Is There Any Role for Sleep Apnea? Hypertension, June 1, 2007; 49(6): e39 - e39. [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||