Published online before print January 23, 2006, doi: 10.1161/01.HYP.0000202480.06735.82
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(Hypertension. 2006;47:434.)
© 2006 American Heart Association, Inc.
Original Articles |
Effect of Salt on Isoprostanes in Salt-Sensitive Essential Hypertension
From the Department of Pharmacology (C.L.L., F.E.), New York Medical College, Valhalla, NY; and Department of Physiology and Biophysics (R.J.B., J.C.R.), Mayo School of Medicine, Rochester, Minn.
Correspondence to Dr Cheryl L. Laffer, Dept of Pharmacology, New York Medical College, Valhalla, NY 10595. E-mail claffer{at}alumni.caltech.edu
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Abstract |
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The controversy over beneficial versus harmful effects of salt on cardiovascular outcomes may be caused by different effects of salt on intermediate phenotypes of hypertension not characterized in epidemiological studies. Hence, we investigated acute effects of salt on oxidative stress in hypertensive subjects classified as salt sensitive (SS, n=14) or salt resistant (SR, n=13) by an inpatient protocol of salt loading (460 mmol NaCl) and salt depletion (10 mmol NaCl and furosemide). Oxidative stress was assessed by measuring the plasma isoprostane 8-iso-PGF2
. SS had lower plasma renin activity, higher aldosterone/renin ratios, and exaggerated endothelin and catecholamine responses to salt depletion compared with SR. Baseline lipid-bound isoprostanes (749±70 pmol/L) were 83% of the total and were slightly but not significantly higher in SS than SR. Baseline free isoprostanes did not differ between groups. After salt loading, lipid-bound isoprostanes were higher in SS (945±106) than SR (579±57; P<0.01). Salt depletion significantly decreased them in SS (–174±84) and increased them in SR (+129±58), equalizing their levels (771±61 versus 708±91; P value not significant). Free isoprostanes were decreased by salt depletion only if data in all of the patients were analyzed together. Total isoprostanes followed the pattern of the lipid-bound fraction. Correlations between salt depletion-induced changes in lipid-bound isoprostanes, plasma renin activity (r=0.45; P<0.02), and aldosterone/renin ratios (r=–0.41; P<0.04) suggested that the more SS the patient, the greater the reduction of oxidative stress by salt depletion. Our research is the first to show that salt affects oxidative stress acutely in humans, particularly in SS hypertension, which may explain the controversial results of epidemiological studies on salt and morbidity and may have implications for therapy.
Key Words: hypertension, essential • hypertension, sodium dependent • oxidative stress • prostaglandins • sodium • human
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Introduction |
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There is overall agreement that salt intake is a major determinant of population blood pressure (BP) and prevalence and severity of hypertension.1 In contrast, there is major disagreement about the effects of salt on cardiovascular outcomes. Many studies have shown that salt is a cardiovascular risk factor independent of BP2,3 and that it relates to left ventricular mass,4 stroke,5 conduit artery stiffness,6 renal disease,7 and cardiovascular morbidity and mortality.8 However, others have reported that salt depletion, rather than salt, is associated with the highest incidence of myocardial infarction and total cardiovascular events in hypertensive patients,9 perhaps because of activation of the renin-angiotensin system.10
Two large epidemiological studies, conducted by different groups on the same database (National Health and Nutrition Examination Survey I), provided a clue to the reason underlying this controversy. Although one of them reported highest all-cause mortality for the lowest salt intake,11 the other found an opposite, direct relationship between salt intake and all-cause and cardiovascular mortalities.12 The major difference between these 2 studies was that the latter gave due consideration to the possibility that 1 hypertensive phenotype (ie, obesity) determined the role of salt on mortality. Hence, it is likely that conflicting results of epidemiological research reflect opposite effects of salt in hypertensive subjects with many different intermediate phenotypes that have not been characterized in these studies. This is supported by the observation that salt sensitivity of BP carries prognostic implications.13
We speculated that the hypertensive intermediate phenotype most likely to be differentially affected by salt in terms of prognosis is that of salt-sensitive (SS) versus salt-resistant (SR) hypertension. In experimental SS hypertension, high salt intake produces increased renal,14–17 myocardial,17,18 vascular,19 and hepatic20,21 oxidative stress, which can be detected by serum markers.17,22 Because in these animal models antioxidants prevent the rise of BP, improve established hypertension,19,20 and ameliorate renal and vascular damage,16,19,22 it is likely that oxidative stress mediates their hypertension and target organ damage.
Therefore, we investigated the prevailing level of and the effect of salt on oxidative stress in SS and SR hypertensive patients, using measurements of the isoprostane 8-iso-prostaglandin (PG)F2, which is a sensitive and specific marker for oxidative stress in experimental models23 and human disease.24
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Methods |
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After protocol approval by the Institutional Review Board and subjects’ informed consent, 27 hypertensive patients (systolic BP >140 mm Hg, diastolic >90 mm Hg, or on antihypertensive treatment) were recruited to undergo determination of salt sensitivity of BP with the protocol validated by Weinberger et al.25 Briefly, after 2 weeks off therapy and on usual salt intake, patients were admitted to the Clinical Research Center where they underwent 24-hour salt loading (160 mmol NaCl diet +2L intravenous saline 8:00 AM to 12:00 PM) followed by 24-hour salt depletion (10 mmol NaCl diet and 40 mg oral furosemide at 8:00 AM, 12:00 PM, and 4:00 PM).
Casual baseline BP was measured before admission with mercury sphygmomanometers (seated, after 5 minutes resting, in triplicate). Ambulatory monitors (Spacelabs 90207) were used to measure BP during admission (every 15 minutes, from 12:00 PM to 10:00 PM, on both protocol days). Patients were classified as SS if the average systolic BP of the salt-depletion day was 
10 mm Hg lower than that of the salt-loading day.
Body mass index (in kg/m2), routine laboratory tests, plasma lipids, and an ECG were obtained at baseline. Left ventricular hypertrophy was diagnosed if the Cornell index [(RaVL+SV3)mmxQRSms] was >2440.
Hormones, vasoactive substances, and isoprostanes were measured at baseline (8:00 AM of the first day, before high-salt diet and saline infusion), after the salt-loading period (8:00 AM of the second day, before furosemide and low-salt diet), and after salt depletion (8:00 AM of the third day, at the end of the protocol). Measurements included plasma renin activity (PRA), plasma aldosterone, and plasma endothelin by previously described radioimmunoassays26–28 and plasma catecholamines by radioenzymatic assay (BioTrak TRK 995, Amersham).
Plasma isoprostanes (free and total) were measured with a previously described enzymatic immunoassay (Cayman Chemical).29 Briefly, blood samples were collected in chilled EDTA tubes, immediately centrifuged at 4°C, and stored at –80°C until assayed. All of the thawed plasma aliquots were eluted in absolute methanol, whereas those for measurement of total isoprostanes were also subjected to 15% KOH hydrolysis (incubation for 1 hour at 38°C) to deesterify the bound fraction. The final eluents were poured into water/buffer solution on ice for pH adjustment to 3.1±0.5. Extraction was performed on Sep-Pak C-18 columns, with washes of water and hexane. Isoprostanes were eluted with 99/1% ethyl-acetate/methanol, dried under nitrogen, and reconstituted into 1.0 mL of assay buffer. Samples and standard were added in triplicate to the assay plate followed by tracer and antibody. After overnight incubation at room temperature and washings with buffer, Ellmans reagent was added. Developed color was read at 405 nm, and values in the sample derived from %B/Bo. The lipid-bound or esterified isoprostane fraction was calculated by subtracting measured free from measured total isoprostanes. Intraassay coefficient of variability was 2.25±0.6% (free) and 12.6±3.8% (total isoprostanes). Interassay variability (several control samples run monthly for 
19 months) was <10%, and the antibody cross reactivity was &20% for 8-isoPGF3 but <4% (mostly <1%) for another 23 prostanoids. The coefficient of variation for the results of this study (35% to 42% in patient subgroups) are well within those reported by others with mass spectrometry30 and by our group with the same method in pigs.29 Twenty-four-hour urine collections were used to assess the effects of the protocol on sodium balance (intake minus urine excretion) during the salt-loading and salt-depletion periods.
Data are presented as mean±SEM. Comparisons between means were made with unpaired t tests; changes within groups were analyzed with paired t tests and correlation coefficients with Pearson’s method. These tests and single linear regression analyses were carried out with JMP software (version 3.2.6, SAS Institute). A P value <5% was used to reject the null hypothesis.
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Results |
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Patients were 46±2 years of age, predominantly women (74%), with slightly more than half being black (56%). Although average baseline BP was within stage I of the Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure classification (152±4/93±2 mm Hg), 30% of patients had systolic BP >160 mm Hg and diastolic BP >100 mm Hg. Obesity (body mass index >30 kg/m2) was present in 70% and current smoking in 37%. Elevated low-density lipoprotein cholesterol (for risk-tailored goal levels of 3.4 or 2.6 mmol/L) and decreased high-density lipoprotein cholesterol (below sex-dependent minimum normal values of 1.3 or 1.0 mmol/L) were present in 31% and 56% of subjects, respectively, whereas triglycerides were elevated (>1.7 mmol/L) in 35%. No patient had significant renal dysfunction (mean creatinine clearance 131±7 mL/min; range, 73 to 200 mL/min), and only 19% had left ventricular hypertrophy by ECG. There were no significant differences in any of these demographic and clinical characteristics between the SS and SR groups (Table 1).
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Using the 10 mm Hg cutoff for a fall in systolic BP from the salt-loaded to the salt-depleted state, 14 subjects were classified as SS (
systolic BP=–13.5±1.4 mm Hg; P<0.001) and 13 as SR ( systolic BP=–3.4±1.1 mm Hg; P value not significant). Table 2 shows that SS patients exhibited many of the previously described characteristics of this intermediate phenotype, including low PRA,31,32 lack of suppression of aldosterone by a salt load,32,33 high aldosterone/renin ratios (ARR),32,34 and exaggerated responses of plasma endothelin35 and catecholamines32,36 to salt depletion. These differences were present despite the fact that the positive salt balance after salt loading (+132±21 mmol/24 h) and the negative one after salt depletion (–181±22 mmol/24 h) were not significantly different between the SS and SR groups (not shown).
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In the 27 patients, baseline plasma level of total isoprostanes, measured before diet manipulation, that is, after patients had been on their ad libitum salt intake, was 903±71 pmol/L. The free isoprostane fraction was 17% of the total (154±24), whereas the calculated lipid-bound fraction constituted the remaining 83% (749±70). At this stage, lipid-bound and total isoprostanes were slightly but not significantly higher in SS than in SR (Figure 1). Levels of free isoprostanes were very similar in both groups.
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and those in SR patients are given by 
. There were no statistically significant differences in isoprostanes between the 2 groups of patients.The absolute levels of lipid-bound and free isoprostanes in SS and SR groups over the 3 conditions of the experiment are compared in the left panels of Figure 2, whereas the magnitude and statistical significance of the changes produced by salt loading and salt depletion are given on the right. Free isoprostanes were not different between SS and SR in any of the 3 conditions of salt balance (Figure 2, bottom left). Although there was an apparent trend toward reduction of free isoprostanes by salt depletion in both groups (Figure 2, bottom right), it did not reach statistical significance unless the 27 patients were analyzed together (–35±21 pmol/L; P<0.05).
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and 
P<0.03. Lack of a statistical symbol indicates lack of statistical significance for either within- or between-group comparisons.Changes induced by salt loading on lipid-bound isoprostanes were of opposite direction (an increase of 93±111 in SS versus a decrease of –60±81 in SR; Figure 2, top right) leading to significantly higher bound isoprostane levels in SS than in SR in the salt-replete state (945±106 versus 579±57; P<0.01; Figure 2, top left). Salt-induced changes in total isoprostanes followed the same pattern (data not shown), most likely because of the fact that the lipid-bound fraction constitutes 83% of the total. Hence, total isoprostanes were also higher in SS than in SR in the salt-replete state (1085±102 versus 746±74 pmol/L; P<0.02).
Salt depletion produced statistically significant changes of opposite direction to those produced by salt loading in both groups. Hence, lipid-bound isoprostanes of SS were significantly reduced by salt deprivation, –174±84 pmol/L (P<0.03), whereas those of SR were significantly increased by 129±58 pmol/L (P<0.03). The difference between these 2 significant changes of opposite direction was also statistically significant by unpaired comparison (Figure 2, top right). As a consequence of these changes, the levels of lipid-bound isoprostanes of SS and SR in the salt-depleted state (771±61 versus 708±91 pmol/L; P value not significant) were not only very similar but closer to each other than those observed when the patients were on ad libitum salt intake during the baseline period; 852±102 and 638±88, respectively (Figure 2, top left). This suggests that our patients’ unmeasured usual salt intake (before the experiment) was closer to that of the salt replete than to that of the salt-depleted period of the protocol. Again, total isoprostanes followed the same pattern as that of the bound fraction (data not shown), with values in the salt-depleted state being 888±60 in SS and 826±92 in SR, not significantly different and closer between groups than those during ad libitum salt intake (998±103 and 802±94, respectively).
We explored whether the response of bound isoprostanes to salt-depletion (ie, the major difference between SS and SR) correlated with any differential biochemical parameters between groups (ie, with any of their distinguishing phenotypic characteristics). Analyzing the 27 patients together, we found no relationship between this response and plasma endothelin, plasma catecholamines, or their stimulation by salt deprivation. In contrast, the change in bound isoprostanes produced by salt depletion correlated with PRA and ARR, such that those patients with more suppressed PRA, hence, higher ARR (both characteristics of our SS patients), had the largest reductions of bound isoprostanes by salt depletion. Figure 3 shows significant regressions for PRA and ARR of the salt-replete state, but similar relationships were present with PRA (r=0.36; P=0.05) and ARR (r=–0.39; P<0.05) of the baseline period (data not shown).
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Analyzing the 2 groups separately, we found no correlation between the reduction of bound isoprostanes and the PRA response to salt depletion of SS (which was blunted, +0.34±0.18 ngAI/L per second). In contrast, the increase of bound isoprostanes and the larger PRA response to salt depletion of SR (+0.74±0.26) were significantly correlated (r=0.70; P<0.001). This difference suggests that the renin-angiotensin system participates in the response of bound isoprostanes to salt depletion, but only in SR, not SS patients.
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Discussion |
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To our knowledge, this is the first report of an acute effect of changes in salt balance on oxidative stress in humans. Discovery of the isoprostanes, PGF2-like compounds formed by free-radical catalyzed, nonenzymatic metabolism of esterified arachidonic acid, has facilitated assessment of oxidative stress in humans, a task that was almost impossible before 1990.37 The compound we measured, 8-iso-PGF2
, is the most abundant F2-isoprostane produced in vivo, has been extensively studied, and is considered to be a sensitive and specific marker for oxidative stress in experimental animals23 and human disease.24 Baseline levels of free and bound isoprostanes in our patients were higher than those reported in normal volunteers.30,38 We cannot state that this represents increased oxidative stress in essential hypertension, because we did not study control subjects, and our measurements were made with a different methodology (enzyme immunoassay) from that used in the published normals (mass spectrometry). However, the proportion of plasma free and bound isoprostanes in our study (17% versus 83%) was similar to that obtained with mass spectrometry in normals (23% versus 77%).30 Also, there are published reports of increased plasma lipid hydroperoxides in malignant and nonmalignant hypertensive patients39 and of increased urinary excretion of isoprostanes in essential hypertensive subjects with concomitant obesity and dyslipidemia,38 2 clinical characteristics that were very prevalent in our population.
The most striking observation of our study was that acute changes in salt balance produced qualitatively different effects on plasma isoprostanes in SS versus SR hypertensive subjects. Our major results were that there is increased oxidative stress during the salt-replete state in SS patients compared with SR and that salt depletion reduces it in SS to the extent of abolishing the difference between groups. We do not have an explanation for the reason that these changes were significant in the lipid-bound fraction but absent in the free fraction of plasma isoprostanes. Little is known about the dynamic relationship between these 2 fractions, but stimuli of oxidative stress produce an immediate increase of bound isoprostanes followed by a delayed appearance of the free fraction.23 Therefore, it is conceivable that our different results for these 2 fractions are accounted for by the acute nature of our experimental design. Regardless of these somewhat different results with lipid-bound versus free isoprostanes, we have shown that there is increased oxidative stress in SS essential hypertension, not SR hypertension, during positive salt balance. This confirms our hypothesis, derived from studies in rodents with genetically (Dahl SS)18 or hormonally (DOC-salt)21 determined salt sensitivity of BP in which hypertension and target organ damage are highly dependent on oxidative stress.16,19,20,22
We can only speculate about the mechanism by which salt acutely increases oxidative stress in SS but not in SR hypertension. Clinical characteristics linked previously to increased oxidative stress in humans, such as left ventricular hypertrophy,18 hypercholesterolemia,40,41 obesity, and atherogenic dyslipidemia reflecting insulin resistance42 cannot explain the differences between SS and SR, because they were equally distributed in the 2 groups. We did not assess whether acute salt loading modified serum lipid concentrations, but this is a highly unlikely explanation for our results, because large differences in salt intake sustained for 30 days failed to modify lipid fractions in the participants of the Dietary Approaches to Stop Hypertension (DASH) sodium study.43
Changes of isoprostanes by salt depletion correlated with PRA in a fashion suggestive of more oxidative stress in patients with renin suppression. This observation may seem paradoxical, because angiotensin II is a major stimulus for oxidative stress44 via actions on membrane assembly of NADPH oxidase subunits.45 However, it has been suggested that oxidative stress plays a role in hypertension at both ends of the salt balance spectrum,46 that is, when the renin-angiotensin system is either stimulated or suppressed. For example, urinary excretion of isoprostanes and malonyldialdehyde of Sprague-Dawley rats can be increased by high-salt diet47 or angiotensin II infusion48 via stimulation of different NADPH oxidase subunits. Moreover, regulation of oxidative stress induced by angiotensin and salt may also be different. For example, angiotensin II stimulates,48 whereas salt inhibits47 mitochondrial superoxide dismutase. It is, therefore, clear that both angiotensin II and salt can stimulate oxidative stress, albeit by different molecular mechanisms.
Only 2 of our 27 patients had PRA >1.39 ngAI/L per second (5 ngAI/mL per hour, the maximum "normal" limit in clinical medicine), whereas 14 had values consistent with "low-renin" hypertension (<0.18 ngAI/L per second or <0.65 ngAI/mL per hour). Hence, it is not surprising that in all patients, lower baseline PRA predicted decreased oxidative stress by salt removal. This suggests that when the renin-angiotensin system is not active, salt may be the major determinant of oxidative stress. In contrast, our SR patients had stimulation of lipid-bound isoprostanes by salt depletion. They had higher baseline PRA and greater PRA stimulation by salt depletion, and the latter correlated with the isoprostane response. This observation may reflect an effect of angiotensin II on the oxidative stress of subjects with preserved regulation of the renin-angiotensin system. Actually, it has been shown recently that angiotensin II infusion fails to stimulate isoprostanes in hypertensive subjects maintained on a low-salt intake.49 This observation, together with our studies, suggests that oxidative stress of essential hypertension may reflect an inappropriate status of salt balance for any degree of activation of the renin-angiotensin system.
Finally, an intriguing possibility is raised by the fact that aldosterone is an independent stimulus for oxidative stress.50 SS hypertensive subjects exhibit an inappropriate lack of suppression of aldosterone in response to a salt load, leading to high ARR.34 In turn, aldosterone and endothelin have been implicated in the target organ damage of SS hypertension in both rodents51,52 and humans.32 Therefore, it is not inconceivable that nonsuppressed aldosterone of SS during positive salt balance is responsible for oxidative stress in these patients. In our experiment, this was supported by the relationship between changes of isoprostanes by salt depletion and ARR, suggesting that oxidative stress is enhanced in patients in whom aldosterone is not suppressed by salt. Once elicited, oxidative stress can, in turn, produce endothelin release.53 Therefore, target organ damage of SS could be mediated via inflammatory effects of aldosterone excess54 and through recruitment of the mitogenic and fibroblast-stimulating actions of both isoprostanes55,56 and endothelin52,57 by aldosterone-induced oxidative stress.
Perspectives
Our observations that salt is capable of acutely increasing isoprostanes in humans and that this phenomenon is peculiar to SS hypertension, have at least 3 major implications. First, we show that isoprostanes, accurate markers of in vivo lipid oxidation that have been used to understand the contribution of oxidative stress to human atherosclerosis, hepatorenal syndrome, and neurodegenerative disorders, are also useful to identify features linked to oxidative stress in essential hypertension, a prevalent disease. This should stimulate research on the kinetics of the relationship between free and esterified isoprostanes and their rates and modes of exchange between compartments (ie, cells, plasma, and urine) for application to future research in humans. Second, we clearly demonstrate different effects of salt on putative mechanisms of target organ damage in at least 1 hypertensive intermediate phenotype. Hence, future epidemiological studies on the effects of salt on cardiovascular outcomes will have to characterize the intermediate phenotypes of the populations studied to resolve the ongoing controversy on the relationship between salt and morbidity. Third, our study shows that it is possible to identify hypertensive subjects in whom oxidative stress may be a major determinant of end-organ damage. Targeting of these subjects in clinical trials of antioxidant therapies may facilitate the discovery of effective agents, an achievement that has been somewhat elusive to date. The possibility that blockers of the mineralocorticoid receptor may constitute specific therapy for hypertension with exaggerated oxidative stress should also be investigated.
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Acknowledgments |
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Supported by National Institutes of Health grants MO1 RR00073 NCRR (to C.L.L., F.E.) and HL-16496 (to J.C.R., R.J.B.).
Received November 3, 2005; first decision November 30, 2005; accepted December 24, 2005.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Stamler J, Rose G, Elliott P, Dyer A, Marmot M, Kesteloot H, Stamler R, for the intersalt Cooperative Research Group. Findings of the International Cooperative Intersalt Study. Hypertension. 1991; 17: I9–15.[Medline] [Order article via Infotrieve]
2. Du Cailar G, Ribstein J, Mimran A. Dietary sodium and target organ damage in essential hypertension. Am J Hypertens. 2002; 15: 222–229.[CrossRef][Medline] [Order article via Infotrieve]
3. de Wardener HE, MacGregor GA. Harmful effects of dietary salt in addition to hypertension. J Hum Hypertens. 2002; 16: 213–223.[CrossRef][Medline] [Order article via Infotrieve]
4. Du Cailar G, Ribstein J, Daures JP, Mimran A. Sodium and left ventricular mass in untreated hypertensive and normotensive subjects. Am J Physiol. 1992; 263: H177–H181.[Medline] [Order article via Infotrieve]
5. Xie JX, Sasaki S, Joossens JV, Kesteloot H. The relationship between urinary cations obtained from the intersalt study and cerebrovascular mortality. J Hum Hypertens. 1992; 6: 17–21.[Medline] [Order article via Infotrieve]
6. Safar ME, Thuilliez C, Richard V, Benetos A. Pressure-independent contribution of sodium to large artery structure and function in hypertension. Cardiovasc Res. 2000; 46: 269–276.
7. Cianciaruso B, Bellizzi V, Minutolo R, Tavera A, Capuano A, Conte G, DeNicola L. Salt intake and renal outcome in patients with progressive renal disease. Miner Electrolyte Metab. 1998; 24: 296–301.[CrossRef][Medline] [Order article via Infotrieve]
8. Tuomilehto J, Jousilahti P, Rastenyte D, Moltchanov V, Tanskanen A, Pietinen P, Nissinen A. Urinary sodium excretion and cardiovascular mortality in Finland: a prospective study. Lancet. 2001; 357: 848–851.[CrossRef][Medline] [Order article via Infotrieve]
9. Alderman MH, Madhavan S, Cohen H, Sealey JE, Laragh JH. Low urinary sodium is associated with greater risk of myocardial infarction among treated hypertensive men. Hypertension. 1995; 25: 1144–1152.
10. Alderman MH, Ooi WL, Cohen H, Madhavan S, Sealey JE, Laragh JH. Plasma renin activity: a risk factor for myocardial infarction in hypertensive patients. Am J Hypertens. 1997; 10: 1–8.[CrossRef][Medline] [Order article via Infotrieve]
11. Alderman MH, Cohen H, Madhavan S. Dietary sodium intake and mortality: the National Health and Nutrition Examination Survey (NHANES I). Lancet. 1998; 351: 781–785.[CrossRef][Medline] [Order article via Infotrieve]
12. He J, Ogden LG, Vupputuri S, Bazzano LA, Loria C, Whelton PK. Dietary sodium intake and subsequent risk of cardiovascular disease in overweight adults. JAMA. 1999; 282: 2027–2034.
13. Weinberger MH, Fineberg NS, Fineberg SE, Weinberger M. Salt sensitivity, pulse pressure, and death in normal and hypertensive humans. Hypertension. 2001; 37: 429–432.
14. Meng S, Roberts LJ, Cason GW, Curry TS, Manning RD Jr. Superoxide dismutase and oxidative stress in Dahl salt-sensitive and -resistant rats. Am J Physiol. 2002; 283: R732–R738.
15. Trolliet MR, Rudd MA, Loscalzo J. Oxidative stress and renal dysfunction in salt-sensitive hypertension. Kidney Blood Press Res. 2001; 24: 116–123.[CrossRef][Medline] [Order article via Infotrieve]
16. Uehara Y, Kawabata Y, Shirahase H, Wada K, Hashizume Y, Morishita S, Numabe A, Iwai J. Oxygen radical scavengers and renal protection by indapamide diuretic in salt-induced hypertension of Dahl strain rats. J Cardiovas Pharmacol. 1993; 22: S42–S46.
17. Umegaki K, Ichikawa T. Vitamin E did not prevent platelet activation, but prevented increase of lipid peroxides and renal dysfunction in DOCA-salt hypertensive rats. J Nutr Sci Vitaminol. 1993; 39: 437–449.[Medline] [Order article via Infotrieve]
18. Somova LI, Nadar A, Gregory M, Khan N. Antioxidant status of the hypertrophic heart of Dahl hypertensive rat as a model for evaluation of antioxidants. Methods Findings Exptl Clin Pharmacol. 2001; 23: 5–12.
19. Beswick RA, Zhang H, Marable D, Catravas JD, Hill WD, Webb RC. Long-term antioxidant administration attenuates mineralocorticoid hypertension and renal inflammatory response. Hypertension. 2001; 37: 781–786.
20. Nicod L, Rodriguez S, Jacqueson A, Viollon-Abadie C, Berthelot A, Richert L. Clofibric acid or diethylmaleate supplemented diet decrease blood pressure in DOCA-salt treated male Sprague Dawley rats-relation with liver antioxidant status. Mol Cell Biochem. 2000; 213: 65–73.[Medline] [Order article via Infotrieve]
21. Nicod L, Rodriguez S, Letang JM, Viollon-Abadie C, Jacqueson A, Berthelot A, Richert L. Antioxidant status, lipid peroxidation, mixed function oxidase and UDP-glucuronyl transferase activities in livers from control and DOCA-salt hypertensive male Sprague Dawley rats. Mol Cell Biochem. 2000; 203: 33–39.[CrossRef][Medline] [Order article via Infotrieve]
22. Atarashi K, Ishiyama A, Takagi M, Minami M, Kimura K, Goto A, Omata M. Vitamin E ameliorates the renal injury of Dahl salt-sensitive rats. Am J Hypertens. 1997; 10: 116S–119S.[Medline] [Order article via Infotrieve]
23. Morrow JD, Awad JA, Kato T, Takahashi K, Badr KF, Roberts LJ II, Burk RF. Formation of novel non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in carbon tetrachloride hepatotoxicity. J Clin Invest. 1992; 90: 2502–2507.[Medline] [Order article via Infotrieve]
24. Morrow JD, Moore KP, Awad JA, Ravenscraft MD, Marini G, Bader KF, Williams R, Roberts LJ II. Marked overproduction of non-cyclooxygenase derived prostanoids (F2-isoprostanes) in the hepatorenal syndrome. J Lipid Mediators. 1993; 6: 417–420.[Medline] [Order article via Infotrieve]
25. Weinberger MH, Miller JZ, Luft FC, Grim CE, Fineberg NS. Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension. 1986; 8-II: 127–134.
26. Sealey JE, Gerten-Banes J, Laragh JH. The renin system: variations in man measured by radioimmunoassay or bioassay. Kidney Intl. 1972; 1: 240–253.[Medline] [Order article via Infotrieve]
27. Antunes JR, Dale SL, Melby JC. Simplified radioimmunoassay for aldosterone using antisera to aldosterone-gamma-lactone. Steroids. 1976; 28: 621–630.[CrossRef][Medline] [Order article via Infotrieve]
28. Schiffrin EL, Thibault G. Plasma endothelin in human essential hypertension. Am J Hypertens. 1991; 4: 303–308.[Medline] [Order article via Infotrieve]
29. Haas JA, Krier JD, Bolterman RJ, Juncos LA, Romero JC. Low-dose angiotensin II increases free isoprostane levels in plasma. Hypertension. 1999; 34: 983–986.
30. Morrow JD, Frei B, Longmire AW, Gaziano JM, Lynch SM, Shyr Y, Strauss WE, Oates JA, Roberts LJ II. Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers: smoking as a cause of oxidative damage. N Engl J Med. 1995; 332: 1198–1203.
31. Rossi E, Regolisti G, Perazzoli F, Negro A, Davoli S, Nicoli D, Sani C, Casali B. 344C/T polymorphism of CYP11B2 gene in Italian patients with idiopathic low renin hypertension. Am J Hypertens. 2001; 14: 934–941.[CrossRef][Medline] [Order article via Infotrieve]
32. Elijovich F, Laffer CL, Schiffrin EL, Gavras H, Amador E. Endothelin-aldosterone interaction and proteinuria in low-renin essential hypertension. J Hypertens. 2004; 22: 573–582.[CrossRef][Medline] [Order article via Infotrieve]
33. Collins RD, Weinberger MH, Dowdy AJ, Nokes GW, Gonzales CM, Leutscher JA. Abnormally sustained aldosterone secretion during salt loading in patients with various forms of benign hypertension: relation to plasma renin. J Clin Invest. 1970; 49: 1415–1426.[Medline] [Order article via Infotrieve]
34. Lim PO, Jung RT, MacDonald TM. Is aldosterone the missing link in refractory hypertension? Aldosterone-to-renin ratio as a marker of inappropriate aldosterone activity. J Hum Hypertens. 2002; 16: 153–158.[CrossRef][Medline] [Order article via Infotrieve]
35. Elijovich F, Laffer CL, Amador E, Gavras H, Bresnahan MR, Schiffrin EL. Regulation of plasma endothelin by salt in salt-sensitive hypertension. Circulation. 2001; 103: 263–268.
36. Campese VM, Romoff MS, Levitan D, Saglikes Y, Friedler RM, Massry SG. Abnormal relationship between sodium intake and sympathetic nervous system activity in salt-sensitive patients with essential hypertension. Kidney Intl. 1982; 21: 371–378.[Medline] [Order article via Infotrieve]
37. Morrow JD, Hill KE, Burk RF, Nammour TM, Bader KF, Roberts LJ II. A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci U S A. 1990; 87: 9383–9387.
38. Stojiljkovic MP, Lopes HF, Zhang D, Morrow JD, Goodfriend TL, Egan BM. Increasing plasma fatty acids elevates F2-isoprostanes in humans: implications for the cardiovascular risk factor cluster. J Hypertens. 2002; 20: 1215–1221.[CrossRef][Medline] [Order article via Infotrieve]
39. Lip GYH, Edmunds E, Nuttall SL, Landray MJ, Blann AD, Beevers DG. Oxidative stress in malignant and non-malignant phase hypertension. J Hum Hypertens. 2002; 16: 333–336.[CrossRef][Medline] [Order article via Infotrieve]
40. Reilly MP, Pratico D, Delanty N, DiMinno G, Tremoli E, Rader D, Kapoor S, Rokach J, Lawson J, FitzGerald GA. Increased formation of distinct F2 isoprostanes in hypercholesterolemia. Circulation. 1998; 98: 2822–2828.
41. Davi G, Alessandrini P, Mezzetti A, Minotti G, Bucciarelli T, Costantini F, Cipollone F, Bon GB, Ciabattoni G, Patrono C. In vivo formation of 8-epi-prostaglandin F2alpha is increased in hypercholesterolemia. Arterioscler Thrombosis Vasc Biol. 1997; 17: 3230–3235.
42. Gopaul NK, Manraj MD, Hebe A, Yan SLK, Johnston A, Carrier MJ, Anggard EE. Oxidative stress could precede endothelial dysfunction and insulin resistance in Indian Mauritians with impaired glucose metabolism. Diabetologia. 2001; 44: 706–712.[CrossRef][Medline] [Order article via Infotrieve]
43. Harsha DW, Sacks FM, Obarzanek E, Svetkey LP, Lin P-H, Bray GA, Aickin M, Conlin PR, Miller ER III, Appel LJ. Effect of dietary sodium intake on blood lipids: results from the DASH-sodium trial. Hypertension. 2004; 43: 393–398.
44. Romero JC, Reckelhoff JF. Role of angiotensin and oxidative stress in essential hypertension. Hypertension. 1999; 34: 943–949.
45. Virdis A, Neves MF, Amiri F, Touyz RM, Schiffrin EL. Role of NAD(P)H oxidase on vascular alterations in angiotensin II-infused mice. J Hypertens. 2004; 22: 535–542.[CrossRef][Medline] [Order article via Infotrieve]
46. Aviv A. Salt consumption, reactive oxygen species and cardiovascular ageing: a hypothetical link. J Hypertens. 2002; 20: 555–559.[CrossRef][Medline] [Order article via Infotrieve]
47. Kitiyakara C, Chabrashvili T, Chen Y, Blau J, Karber A, Aslam S, Welch WJ, Wilcox CS. Salt intake, oxidative stress, and renal expression of NADPH oxidase and superoxide dismutase. J Am Soc Nephrol. 2003; 14: 2775–2782.
48. Chabrashvili T, Kitiyakara C, Blau J, Karber A, Aslam S, Welch WJ, Wilcox CS. Effects of Ang II type 1 and type 2 receptors on oxidative stress, renal NADPH oxidase and SODs expression. Am J Physiol. 2003; 285: R117–R124.
49. Murphey LJ, Morrow JD, Sawathiparnich P, Williams GH, Vaughan DE, Brown NJ. Acute angiotensin II increases plasma F2-isoprostanes in salt-replete human hypertensives. Free Radical Biol Med. 2003; 35: 711– 718.[CrossRef][Medline] [Order article via Infotrieve]
50. Keidar S, Kaplan M, Pavlotzky E, Coleman R, Hayek T, Hamoud S, Aviram M. Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development. Circulation. 2004; 109: 2213–2220.
51. Park JB, Schiffrin EL. ET(A) receptor antagonist prevents blood pressure elevation and vascular remodeling in aldosterone-infused rats. Hypertension. 2001; 37: 1444–1449.
52. Li JS, Lariviere R, Schiffrin EL. Effect of a nonselective endothelin antagonist on vascular remodeling in deoxycorticosterone acetate-salt hypertensive rats: evidence for a role of endothelin in vascular hypertrophy. Hypertension. 1994; 24: 183–188.
53. Michael JR, Markewitz BA, Kohan DE. Oxidant stress regulates basal endothelin-1 production by cultured rat pulmonary endothelial cells. Am J Physiol. 1997; 273: L768–L774.[Medline] [Order article via Infotrieve]
54. Rocha R, Stier CT, Kifor I, Ochoa-Maya MR, Rennke HG, Williams GH, Adler GK. Aldosterone: a mediator of myocardial necrosis and renal arteriopathy. Endocrinology. 2000; 141: 3871–3878.
55. Fukunaga M, Makita N, Roberts LJ II, Morrow JD, Takahashi K, Badr KF. Evidence for the existence of F2-isoprostane receptors on rat vascular smooth muscle cells. Am J Physiol. 1993; 264: C1619–C1624.[Medline] [Order article via Infotrieve]
56. Kunapuli P, Lawson JA, Rokach JA, FitzGerald GA. Functional characterization of the ocular PGF2alpha receptor: activation by the isoprostane 12-epi-PGF2alpha. J Biol Chem. 1997; 272: 27147–27154.
57. Kassab S, Miller MT, Novak J, Reckelhoff J, Clower B, Granger JP. Endothelin-A receptor antagonism attenuates the hypertension and renal injury in Dahl salt-sensitive rats. Hypertension. 1998; 31: 397–402.
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