Salt loading on plasma asymmetrical dimethylarginine and the protective role of potassium supplement in normotensive salt-sensitive asians

Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. Because endothelial NO pathway is compromised in patients with salt-sensitive hypertension, we investigated whether the plasma ADMA can be modulated by chronic salt loading in normotensive salt-sensitive persons and its relationship with NO, and we further determined whether or not dietary potassium supplementation can reverse them. Sixty normotensive subjects (aged 20 to 60 years) were selected from a rural community of Northern China. All of the people were sequentially maintained on a low-salt diet for 7 days (3 g/day, NaCl), then a high-salt diet for 7 days (18 g/day), and high-salt diet with potassium supplementation for another 7 days (4.5 g/day, KCl). After salt loading, the plasma ADMA concentrations increased significantly in salt-sensitive subjects (0.89+/-0.02 micromol/L versus 0.51+/-0.02 micromol/L; P<0.05), whereas the plasma NOx levels reduced considerably (41.8+/-2.1 micromol/L versus 63.5+/-2.1 micromol/L; P<0.01). All of the abnormalities normalized when dietary potassium were supplemented (0.52+/-0.03 micromol/L versus 0.89+/-0.02 micromol/L for ADMA and 58.1+/-0.9 micromol/L versus 41.8+/-2.1 micromol/L for NOx). Statistically significant correlations were found among plasma ADMA level, the mean blood pressure, and the level of NO after salt loading in normotensive salt sensitive individuals. Our study indicates that high dietary potassium intake reduces blood pressure and ADMA levels while increasing NO bioactivity in normotensive salt-sensitive but not salt-resistant Asian subjects after salt loading.     

Nitric oxide inhibition as a mechanism for blood pressure increase during salt loading in normotensive postmenopausal women

OBJECTIVES: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO), which plays an important role in natriuresis. We determined whether changes in endothelium-dependent vasodilation (EDD) and plasma ADMA predict changes in blood pressure (BP) after salt loading in normotensive postmenopausal women (PMW). METHODS: In 15 normotensive PMW (age 50-60 years), not receiving estrogen, ambulatory 24-h BP, plasma lipids, and ADMA were measured after 4 days of a low-salt diet (70 mEq/day) and following 7 days of high-salt intake (260 mEq/day). Brachial artery diameter at rest, during reactive hyperemia, i.e. EDD, and after sublingual nitroglycerin, i.e. non-EDD, were measured by ultrasound. The 24-h urinary NO metabolite (NOx) was measured by Griess reaction. Plasma ADMA was measured by high-pressure liquid chromatography. RESULTS: During low-salt, 24-h BP levels averaged 121 +/- 11 and 69 +/- 7 mmHg for systolic BP (SBP) and diastolic BP (DBP), respectively. After salt loading, average 24-h BP increases were: 7.6 mmHg for SBP, 2.2 mmHg for DBP, and 5.5 mmHg for pulse pressure (PP). Increases of 24-h SBP and 24-h PP after salt loading correlated directly with changes in ADMA (partial R2 = 0.16 for 24-h SBP and 0.17 for 24-h PP, P < 0.05 for both) and inversely with changes in EDD (partial R2 = 0.13, P = 0.09 for 24 h SBP and partial R2 = 0.15, P = 0.07 for 24-h PP), after adjustment for age and cholesterol. CONCLUSIONS: Inhibition of NO bioavailability by ADMA and a subsequent reduction in EDD contribute to the increase in BP during high-salt intake in normotensive PMW not receiving estrogen.     

Amelioration of vascular endothelial dysfunction in obstructive sleep apnea syndrome by nasal continuous positive airway pressure--possible involvement of nitric oxide and asymmetric NG, NG-dimethylarginine.

BACKGROUND: Asymmetric NG,NG-dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase and its plasma concentration is elevated in patients with cardiovascular risk factors, including hyperlipidemia, hypertension, diabetes, and hyperhomocysteinemia. Obstructive sleep apnea syndrome (OSAS) has been attracting attention as a risk factor for cardiovascular disorders because it often accompanies hypertension, obesity, glucose impairment, and dyslipidemia, all of which are factors in metabolic syndrome and risk factors for cardiovascular disease. METHODS AND RESULTS: In the present study, flow-mediated vasodilatation (FMD) of the brachial artery and plasma concentrations of ADMA were measured before and after nasal continuous positive airway pressure (nCPAP) therapy, which abrogates apnea, in 10 male patients aged 36-69 years old, who were given a diagnosis of OSAS by polysomnography. The percent FMD (%FMD) improved significantly from 3.3+/-0.3% to 5.8+/-0.4% (p<0.01) and 6.6+/-0.3% (p<0.01), before, 1 week, and 4 weeks after nCPAP, respectively. At the same time, the plasma NOx concentrations, metabolites of NO, tended to increase, but the plasma ADMA concentration decreased inversely to %FMD and NOx. A negative correlation between %FMD and plasma ADMA concentration, and a positive correlation between %FMD and plasma NOx concentrations were observed. CONCLUSION: Nasal CPAP improves endothelial function, in part by the decreasing ADMA concentration, thereby potentiating NO production.     

Plasma ProANP(1-30) reflects salt sensitivity in subjects with heredity for hypertension

The aim of the present study was to investigate whether plasma concentration of proANP(1-30), the N-terminal fragment of the atrial natriuretic peptide prohormone, or 24-hour urinary excretion of urodilatin reflects the degree of salt sensitivity in hypertension-prone individuals. Plasma concentration of proANP(1-30) and urinary urodilatin excretion were determined at baseline, after 1 week on a low-salt diet (10 mmol/d) and after another week on a high-salt diet (240 mmol/d) in 30 healthy subjects with heredity for hypertension. Salt sensitivity was defined as the difference between mean arterial blood pressure after the high-salt diet and the mean arterial blood pressure after the low-salt diet. High- versus low-salt intake increased proANP(1-30) (668+/-330 versus 358+/-150 pmol/L; P<0.00001) and urodilatin (18.7+/-5.2 versus 16.0+/-8.3 pmol/24 h; P<0.05). ProANP(1-30) correlated with salt sensitivity at baseline (r=0.76, P<0.000001), after the low- (r=0.80, P<0.0000001) and high-salt diets (r=0.85, P<0.00000001). The increase in proANP(1-30) induced by changing from the low- to the high-salt diet was also directly related to salt sensitivity (r=0.78, P<0.000001). ProANP(1-30) was not related to urinary sodium excretion. Neither urodilatin nor the sodium-induced change in urodilatin correlated with salt sensitivity. However, urodilatin was related to the urinary sodium excretion at baseline (r=0.58, P<0.01) and after the high-salt diet (r=0.62, P<0.001). In conclusion, the close correlations between proANP(1-30) and salt sensitivity suggest that proANP(1-30) may serve as a marker for salt sensitivity and could be useful in identifying subjects who would benefit from dietary salt restriction to prevent development of hypertension.     

Salt sensitivity in young normotensive subjects is associated with a hyperinsulinemic response to oral glucose.

Insulin resistance associated with a hyperinsulinemic response to oral glucose intake has been found in patients with essential hypertension and is believed to play a role in inducing hypertension by causing renal sodium and water retention. We therefore examined whether salt-sensitive, young normotensives, assumed to be predisposed to essential hypertension, exhibit impaired glucose tolerance in a similar way. The plasma insulin and glucose response to oral glucose intake (75 g) was assessed in 23 healthy, lean, male volunteers ingesting either 20 mmol or 260 mmol NaCl/day for 6 days each in a single-blind randomized crossover study. Salt sensitivity was defined as a significant drop in mean arterial blood pressure greater than 3 mmHg (means of 30 readings in the supine subject; P less than 0.05) under the low-salt diet. Following the glucose load, plasma levels of both glucose and insulin were significantly higher (P less than 0.01) in the salt-sensitive (n = 10) compared with the salt-resistant subjects (n = 13) during the high-salt diet but not during the low-salt diet. Whereas in the salt-sensitive group glucose tolerance improved with dietary salt restriction (P less than 0.01), it deteriorated in the salt-resistant group (P less than 0.05). Following the glucose load under the high-salt diet, there was a significant drop in blood pressure in the salt-sensitive (P less than 0.005) but not the salt-resistant subjects. The hyperglycemic and hyperinsulinemic response in salt-sensitive subjects suggests that insulin resistance is present in these subjects prior to the development of hypertension and that it can be ameliorated by salt restriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

ADMA: a novel risk factor that explains excess cardiovascular event rate in patients with end-stage renal disease

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase. By competitively displacing L-arginine from the substrate binding site of NO synthase, ADMA interferes with many of the physiological functions of NO, like endothelium-dependent vasodilation and leukocyte adhesion. ADMA, like its biologically inactive regioisomer, symmetric dimethylarginine (SDMA), can be found in human plasma and urine in low concentrations. The concentrations of both dimethylarginines are increased in patients with end-stage renal disease, which may explain at least in part endothelial dysfunction and cardiovascular complications in this patient population. In addition, the metabolism of ADMA, but not SDMA, occurs via hydrolytic degradation to citrulline and dimethylamine by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Data from experimental studies suggest that ADMA inhibits vascular NO elaboration at concentrations that can be measured in plasma of patients with renal disease. Interestingly, ADMA and SDMA are poorly eliminated during hemodialysis. This is probably due to a high level of binding of both molecules to plasma proteins. High ADMA concentrations in patients with end-stage renal disease may contribute to their excess cardiovascular event rate, as in clinical studies a relationship between ADMA and carotid artery intimal thickening was found. Moreover, in a prospective study we demonstrated recently that determination of ADMA plasma concentration is useful to predict future cardiovascular event rate and total mortality in this patient population. As other researchers reported observations that are in line with our findings, there is evidence that ADMA may be a novel cardiovascular risk factor.     

Effect of salt on insulin sensitivity differs according to gender and degree of salt sensitivity

The aim of the present study was to investigate the effect of salt intake on insulin sensitivity and the relation between salt sensitivity and insulin sensitivity in genetically hypertension-prone individuals. Twenty-eight healthy subjects (13 men and 15 women) with a family history of hypertension were examined at baseline, after 1 week of salt restriction (10 mmol/d), and after 1 week of salt loading (240 mmol/d). Insulin sensitivity was measured with the hyperinsulinemic euglycemic clamp after the low- and high-salt diets. Salt sensitivity was defined as the difference in mean arterial blood pressure between the high-salt and the low-salt diets. There was no significant relationship between insulin sensitivity and salt sensitivity after either of the 2 diets. In the men, salt sensitivity was inversely related to plasma renin activity (r=-0.61, P=0.03) and plasma aldosterone (r=-0.74, P=0.004), whereas salt sensitivity in women was directly correlated with the salt-induced increase in body weight (r=0.68, P=0.005). In men, the high-salt diet induced a change in glucose disposal that was strongly correlated with the degree of salt sensitivity (r=0.83, P=0. 0004), plasma renin activity (r=-0.82, P=0.0006), and plasma aldosterone concentrations (r=-0.87, P=0.00009) (eg, the greater the salt sensitivity and the lower the activity of the renin-angiotensin-aldosterone system, the greater improvement in insulin sensitivity). No such relationships were observed in women. In conclusion, increased salt sensitivity and decreased activity of the renin-angiotensin-aldosterone system predict improved insulin sensitivity with high-salt intake compared with low-salt intake in men, suggesting an interaction among salt intake, salt sensitivity, the renin-angiotensin-aldosterone system, and insulin action.     

Endothelial damage,asymmetric dimethylarginine and cardiovascular risk in end-stage renal disease

To be appropriately labelled as a 'risk factor' any putative risk factor should increase the prediction power of standard statistical models based on 'traditional' (Framingham) risk factors. In end-stage renal disease (ESRD), Framingham risk factors do not fully explain the cardiovascular burden of these patients. Inflammation, hyperhomocysteinemia and anemia contribute to the high cardiovascular risk of ESRD, but knowledge is still incomplete. We suspected that asymmetric dimethylarginine (ADMA) is an important cardiovascular risk factor in dialysis patients. This substance inhibits nitric oxide synthase thus triggering a series of pathophysiological events leading to atherosclerosis. To test this hypothesis, we studied the relationship between ADMA and intima media thickness (IMT) in the carotid artery. ADMA was found to be strongly and independently related to IMT. More importantly we found that patients with relatively higher plasma ADMA had shorter survival and a higher rate of incident cardiovascular complications in comparison to those with a relatively lower plasma concentration. These data represent a sound basis for intervention studies aimed at modifying the plasma ADMA concentration in ESRD patients.     

Significance of sympathetic nervous system in sodium-induced nocturnal hypertension.

OBJECTIVE: The purpose of this study was to investigate the effects of salt loading on circadian patterns of blood pressure (BP) and sympathetic nervous activity. SUBJECTS AND METHODS: Seventy-six patients with essential hypertension were hospitalized and placed on a low-salt diet (2 g/day) for 7 days followed by a high-salt diet (20-23 g/day) for another 7 days. On the last day of each salt diet, 24 h ambulatory BP, plasma noradrenaline concentrations, urinary noradrenaline excretion, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured. Patients whose average mean BP was increased by more than 10% by salt loading were assigned to the salt-sensitive (SS) group (n = 44); the remaining patients, whose mean BP was increased by less than 10%, were assigned to the non-salt-sensitive (NSS) group (n = 32). RESULTS: Salt loading converted the circadian pattern of BP from dippers, whose mean BP during the night-time was decreased by more than 10% from the daytime BP, to non-dippers in the SS group but not in the NSS group. A nocturnal decrease in plasma noradrenaline concentration was unaffected after salt loading in the NSS group but dampened in the SS group. The night-time/daytime ratio of urinary noradrenaline excretion, which was increased after salt loading in the SS group only, was greater in the SS group than in the NSS group under the high-salt diet. The salt-induced suppression rate of PRA and PAC was similar between the SS and NSS groups. CONCLUSION: BP fails to fall during the night under the high-salt diet in patients with the SS type of essential hypertension. This may be related to the lack of nocturnal decrease in sympathetic nervous activity.     

Asymmetric dimethylarginine (ADMA): a cardiovascular and renal risk factor on the move

The endogenous inhibitor of the nitric oxide synthase, asymmetric dimethylarginine (ADMA), by reducing nitric oxide (NO) availability, may trigger pro-atherogenic effects. A high plasma concentration of this substance has been associated to intima-media thickening, left ventricular hypertrophy and all-cause and cardiovascular mortality in patients with end-stage renal disease, and to coronary events in males in the general population. Recent studies show that ADMA predicts renal disease progression and death in patients with moderate to severe renal insufficiency. ADMA may be at the crossroad of the atherosclerosis process and may represent an important factor in the high risk associated with renal insufficiency.     

Circulating coupling factor 6 in human hypertension: role of reactive oxygen species

OBJECTIVE: Coupling factor 6 is an endogenous inhibitor of prostacyclin synthesis and might function as an endogenous vasoconstrictor in the fashion of a circulating hormone in rats. We investigated the role of coupling factor 6 in human hypertension. METHODS AND RESULTS: The patients with essential hypertension (EH) (n = 30) received a series of normal salt diet (12 g salt/day) for 3 days, low salt diet (2 g salt/day) for 7 days, and high salt diet (20-23 g salt/day) for 7 days. Normotensive control subjects (n = 27) received normal and low salt diets. The plasma level of coupling factor 6, measured by radioimmunoassay, during normal salt diet was higher in patients with EH than in normotensive subjects (17.6 +/- 1.7 versus 12.8 +/- 0.5 ng/ml, P < 0.01). Whereas the plasma level of coupling factor 6 was unchanged after salt restriction in normotensive subjects, it was decreased after salt restriction (from 12 g/day to 2 g/day) and was increased after salt loading (from 2 g/day to 20-23 g/day) in patients with EH. This increase in plasma level of coupling factor 6 was abolished by oral administration of ascorbic acid, but the level of blood pressure was unaffected. The percentage changes in plasma coupling factor 6 level after salt restriction and loading were positively correlated with those in mean blood pressure (r = 0.57, P < 0.01), and negatively correlated with those in plasma nitric oxide level (r = -0.51, P < 0.05). CONCLUSION: These indicate that circulating coupling factor 6 is elevated in human hypertension and modulated by salt intake presumably via reactive oxygen species.     

Arguments For The Presence of A Na-K ATPase Pump Inhibitor in The Plasma of Uremic and Essential Hypertensive Patients

The effect of salt and/or volume depletion has been tested in 6 end-stage renal disease and 11 essential hypertensive patients (HTA) on red blood cell (RBC) ionic fluxes. Volume depletion promotes an increase in the RBC Na-K ATPase activity with, as a result, a significant decrease in intracellular sodium concentration ((Na)ic). Moreover, a factor has been found in the plasma of uremic subjects which causes natriuresis when injected in rat renal arteries. The concentration of this factor decreases during dialysis in relation to the weight loss and the increase in the RBC Na-K pump activity. In essential hypertension, the effect of a low salt diet on the blood pressure is correlated with the improvement of RBC Na-K ATPase activity. These experiments illustrate the presence of a Na-K ATPase inhibitor in the plasma of these subjects, dependent on sodium and water balance.     

Adrenomedullin: Changes in Circulating and Cardiac Tissue Concentration in Dahl Salt-Sensitive Rats on a High-Salt Diet

Adrenomedullin (AM), a novel hypotensive peptide, is suggested to be involved in defense mechanisms against hypertension, however, the detail mechanisms have not been clarified. To elucidate whether AM synthesis would be altered in a salt dependent hypertension, we have investigated the AM concentration and AM messenger RNA (mRNA) level in tissues of Dahl salt-sensitive rats on either low-or high-salt intake. The AM concentration in cardiac ventricle of the high-salt group was significantly higher than that of the low-salt group. The plasma AM concentration was also significantly higher in the high-salt group than in the low-salt group. Furthermore, the plasma AM concentration correlated well with the weight of left ventricle. RNA blot analysis revealed that the AM mRNA level in cardiac ventricle of the high-salt group was higher than that of the low-salt group. These results suggest that AM participates in the pathophysiology of salt dependent hypertension and plays a role in cardiac hypertrophy.     

Sympathetic activation enhances QT prolongation by quinidine

INTRODUCTION: Salt restriction results in endogenous sympathetic activation, and we previously showed that plasma concentrations of quinidine measured after oral drug administration are increased during a low-salt diet. However, it is not known whether, independent of effects on plasma concentration, the extent to which quinidine prolongs the QT interval also is modulated by changes in endogenous sympathetic activity. METHODS AND RESULTS: In these studies, we evaluated quinidine concentration-QT relations during low-salt (10 mEq/day for 8 days) and high-salt (400 mEq/day for 8 days) diets, with or without beta blockade in normal volunteers. In the absence of beta blockade, the concentration producing a fixed (15%) increase in QTc was significantly lower with salt restriction: 1.2 +/- 0.4 microg/mL (low salt) versus 2.2 +/- 0.4 microg/mL (high salt) (P < 0.01). With beta blockade, this difference was abolished: 1.9 +/- 0.3 microg/mL (low salt + beta blockade) versus 2.1 +/- 0.3 microg/mL (high salt + beta blockade). QT morphologic abnormalities including bifid T waves and U waves were abolished with beta-adrenergic blockade. CONCLUSION: Sympathetic activation by a low-salt diet not only modulates drug disposition but also increases sensitivity to drug-induced QT prolongation.     

Endothelial dysfunction in normotensive salt-sensitive subjects

Salt-sensitivity is associated with a more severe target organ injury and higher mortality, even in normotensive subjects. As endothelial dysfunction is predictive for future cardiovascular events, we evaluated whether normotensive salt-sensitive (NSS) subjects have more pronounced endothelial dysfunction compared with normotensive salt-resistant (NSR) subjects. Normotensive subjects (n=99, aged 25-50 years) were selected from a rural community in northern China. Salt sensitivity was assigned if mean BP increased by ≥10% from a 1-week high salt (18?g/day, NaCl) to low-salt diet (3?g/day, NaCl). Endothelial function was assessed by testing the flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, as well as nitrogen oxide (NOx) levels, in plasma and urine at baseline. Blood pressure at baseline was similar between NSS and NSR subjects, but diverged during salt intervention. Furthermore, FMD was significantly lower in 17 NSS subjects (10.2±2.5 vs 14.5±1.6%, P=0.037) compared with NSR subjects. In addition, average plasma NOx levels were lower in NSS subjects than NSR subjects (61.2±3.23?μM vs 82.5±1.61?μM, P=0.034). Moreover, Both FMD and plasma NOx levels were negatively correlated with the degree of salt sensitivity (r=-0.435 and r=-0.459, respectively, P<0.01). However, there was no difference in urine NOx between the two groups. Our study indicates that endothelial dysfunction could contribute to the long-term higher levels of target organ injury and higher mortality observed in NSS subjects.     

慢性盐负荷对血压盐敏感者血浆内皮生长因子C的影响

目的 本研究通过对正常血压受试者进行饮食干预试验,观察高盐对盐敏感者血浆内皮生长因子C(VEGF-C)的影响,探索淋巴系统在盐敏感性形成过程中的作用。方法对27例血压正常受试者进行7 d低盐、7 d高盐饮食干预,采用国际慢性盐负荷试验鉴别盐敏感者,筛选出盐敏感者9例,盐不敏感者18例,采用ELISA方法测定血浆VEGF-C的含量。结果两组受试者低盐期血浆VEGF-C水平比较无统计学差异〔(1921±238) mg/L vs.(1804±206) mg/L,P=0.59〕,而高盐干预后两组血浆VEGF-C水平均较低盐期明显增加〔盐敏感组(3642±406) mg/L,盐不敏感组(2249.8±214.6) μg/ml〕,并且高盐干预后盐敏感组VEGF-C水平较盐不敏感组显著升高（P<0.01）;相关分析表明,血浆VEGF-C水平与血压之间未发现具有统计学意义的相关性（r=0.412,P=0.29）。结论高盐饮食后盐敏感者体内VEGF-C显著升高,而VEGF-C可能成为盐敏感性识别的重要生化标记物之一。     

Hypertension and obesity in rats with ventromedial-hypothalamic lesions and low salt intake

The arterial hypertension that frequently coexists with ventromedial hypothalamic (VMH) lesion-induced obesity has been obtained in rats chronically sustained on diets of standard-to-high salt content. Since VMH lesions also compromise the renal circulation and enhance ingestion of salt-loaded diets, the resulting haemodynamic adjustments, including hypertension, have been interpreted as possibly being sodium-dependent. This notion implies that chronically restricting dietary salt would ameliorate the hypertension, whereas the persistence of hypertension under such a regiment would suggest the potential contribution of non-sodium-related factors. This study assessed whether chronic maintenance of a low-salt diet would buffer the hypertensive and haemodynamic consequences of obesity, accompanying electrolytic VMH lesions in male Wistar-Kyoto (WKY) rats, compared with sham-treated controls. Despite the low-salt diet, the results showed that VMH obesity was accompanied by hypertension, elevated plasma norepinephrine, and redistribution of blood flow away from the brain, kidney and splanchnic organs. The compatibility of these results with earlier studies permitting salt ingestion, is difficult to reconcile with the notion that VMH-hypertension is sodium-dependent. Instead, it suggests that the VMH obesity-hypertension syndrome may provide a useful model for clarifying the autonomic consequences of either augmented carbohydrate ingestion of hyper-insulinaemia.     

Increased concentration of plasma immunoreactive atrial natriuretic factor in Dahl salt sensitive rats with sodium chloride-induced hypertension

In order to determine whether there is a relationship between genetically determined salt-induced hypertension and atrial natriuretic factor (ANF), a radio-immunoassay for ANF was applied to the determination of immunoreactive ANF in plasma, atrium, hypothalamus and pons of Dahl salt-sensitive (S) and -resistant (R) rats which were fed high- or low-salt diet for 7 weeks. A twofold higher concentration of plasma ANF was observed in high-salt S rats, which developed hypertension, compared with low-salt S rats or R rats on high or low salt, which were normotensive. No significant difference was seen in atrial concentrations of ANF between S and R rats. The brain ANF concentration of the high-salt group was lower than that of the low-salt group in both S and R rats. It is proposed that the elevation of plasma ANF in the hypertensive rats may reflect a compensatory mechanism induced by volume expansion in the salt-fed S rats.     

Effect of dietary sodium in hypertension not treated with drugs]

The usefulness of salt restriction in essential hypertension is still now disputed. This study was designed to test the influence of a diet with and without salt restriction in 19 untreated essential hypertensives (12 with and 7 without family history of hypertension) and free of cardiovascular and renal complications. Each patient was examined after a placebo period, after 1 month of salt restriction, and after 1 month of salt supplementation. Weight, blood pressure, 24 hours urinary sodium excretion and red blood cell ionic fluxes were measured. In patients with hypertensive heredity, the blood pressure did not change. The intracellular sodium concentration, the cotransport and the countertransport remained stable. The ouabain sensitive sodium pump slightly increased during salt restriction and remained stable after salt supplementation. In patients without such hypertensive heredity (who were older and heavier), sodium restriction period was characterized by significant decrease in blood pressure, weight, intracellular sodium concentration and increase in sodium pump activity. When salt was increased, all the parameters remained stable. A more balanced diet with sodium restriction decreases the blood pressure in relation to age, weight and the blood pressure level. Hypertensive heredity does not seem to be a parameter of salt sensitivity. The blood pressure decrease is also related to the quantitative importance of sodium restriction. The ouabain sensitive pump activity changes during diet especially in relation to weight loss and decreasing salt intake.     

Abnormal renal hemodynamics in salt-sensitive patients with essential hypertension

Thirty hypertensive patients were studied during a low-sodium diet for three days and a high-sodium diet for six days. They were classified as "salt-sensitive" (SS) (n = 10) or "non-salt-sensitive" (NSS) (n = 20) based on the increase in mean blood pressure (BP) with changes in sodium intake from 25 mEq/day to 250 mEq/day (14.7 +/- 1.3% versus 4.0 +/- 0.8%, p less than 0.001). With the high-sodium diet, the SS patients had a greater increase in cardiac output (p less than 0.001), and the increment in mean BP with the salt loading significantly correlated to that in cardiac output (r = 0.672, p less than 0.01). Thus, the increase in BP during short-term salt loading may be attributed to the increase in cardiac output. The role of renal hemodynamics in the increment of BP with salt loading after sodium restriction was evaluated in six SS and 14 NSS patients. Although the glomerular filtration rate was not different in the two groups, the renal vascular resistance was greater (p less than 0.05) in the SS patients than in the NSS ones. Moreover, renal vascular resistance positively correlated to the increment in mean BP with salt loading (r = 0.612, p less than 0.01). Thus, it is suggested that renal vasoconstriction may be an important factor influencing "salt-sensitivity" in essential hypertension, possibly via the impaired renal sodium excretion.