Insulin resistance in young salt-sensitive normotensive subjects.

Insulin resistance has been demonstrated in patients with essential hypertension, and insulin-mediated sodium retention is believed to contribute to hypertension in these individuals. Recently, a hyperinsulinemic response to an oral glucose load has been found in salt-sensitive normotensive subjects, suggesting that insulin resistance may be present in these hypertension-prone individuals before the development of hypertension. In the present study, we examined the relation between insulin sensitivity and blood pressure response to salt intake in young, lean normotensive subjects on a high and a low salt diet. Insulin sensitivity was estimated by the "insulin suppression test," i.e., by measuring the plasma glucose and insulin concentrations achieved during a 180-minute infusion of somatostatin, insulin, and glucose in 18 healthy male volunteers (age, 21-28 years) given a standardized low salt diet (20 mmol/day) for 2 weeks, supplemented by either 220 mmol of NaCl per day or placebo in a single-blind randomized order for 1 week each. We defined salt sensitivity as a significant decrease in mean arterial blood pressure (> 3 mm Hg [p < 0.05]) measured for 60 minutes at 1-minute intervals on the low salt diet. By this definition, seven of the 18 subjects were salt sensitive. Although insulin infusion resulted in similar plasma insulin levels (approximately 50 milliunits/L) in both groups, concomitant glucose infusion resulted in plasma glucose levels that were more than 50% higher in the salt-sensitive than in the salt-resistant group (p < 0.005 by two-way analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)

Resting metabolic rate and substrate use in obesity hypertension.

There is substantial evidence that obesity is a prime risk factor for the development of hypertension. Although hyperinsulinemia and an increased activity of the sympathetic nervous system have been implicated in the pathogenesis of "obesity hypertension," their effects on energy metabolism have not been studied thus far. In the present study, we therefore examined resting metabolic rate (RMR) and basal substrate oxidation in subjects with obesity and obesity-related hypertension. A total of 166 subjects were characterized for RMR and basal substrate use through indirect calorimetry. Blood pressure was measured at rest and with 24-hour ambulatory monitoring. Blood samples were collected for the measurement of plasma catecholamines, leptin, and the insulin response to an oral glucose load. In our study population, 116 subjects were defined as hypertensive and 91 were defined as obese. Hypertensive patients under beta-adrenergic blockade (n=42) had a significantly lower RMR than did patients without beta-blockade (P<0. 05) and were therefore excluded from further analyses. Univariate regression analysis revealed a significant relationship between RMR and body fat mass, as well as body fat-free mass, in both groups. Compared with obese normotensive control subjects (n=27), obese hypertensives (n=43) had a 9% higher RMR (P<0.05), higher plasma catecholamine (P<0.05) and leptin (P<0.05) levels, and an increased insulin response to oral glucose (P<0.01). Together, these findings are compatible with the idea that chronic neurogenic and metabolic adaptations related to obesity may play a role in the development of obesity hypertension in susceptible individuals.

Identification of a renin threshold and its relationship to salt intake in a patient with pure autonomic failure.

Animal studies have demonstrated a threshold below which renin release increases proportionally to a decrease in renal perfusion pressure. Demonstration of a similar mechanism in humans, however, has proved difficult, as any attempt to lower blood pressure below the putative renin threshold results in renin release mediated by reflex activation of the sympathetic nervous system. In this study, we report on our observations in a 71-year-old woman who presented with a 20-year history of faintness and syncope and was diagnosed as having pure autonomic failure. Graded head-up tilting resulted in a stepwise reduction in mean arterial blood pressure to a minimum of 54 mm Hg, with no signs of increased sympathetic activity. A fall in blood pressure below 80 mm Hg resulted in a distinct rise in plasma renin activity, and a similar threshold pressure was observed under both a 50- and a 100-mmol/d sodium chloride diet. Below the threshold, response to changes in perfusion pressure was proportionally greater under the 50-mmol/d diet than under a 100- or 200-mmol/d diet. These observations demonstrate that a pressure threshold for renin release at 10 to 15 mm Hg below ambient blood pressure, as described previously in animal studies, is also present in humans. The significance of this pressure-dependent mechanism of renin release for the long-term regulation of blood pressure and water and mineral balance in humans remains to be determined.

Renal acid-base excretion in normotensive salt-sensitive humans.

Reduced extracellular pH and bicarbonate levels recently have been reported in normotensive salt-sensitive subjects. To assess the possible role of altered renal acid-base handling in the perturbation of acid-base status in these individuals, we measured the renal acid-base excretion after an acute oral administration of either an alkali or acid load in normotensive salt-sensitive and salt-resistant men. Twenty-four young (22 to 29 years old), healthy male volunteers were placed on a low-salt diet (20 mmol NaCl per day) for 2 weeks with either 220 mmol NaCl or placebo added to the low-salt diet for 1 week each in a randomized single-blind crossover order. Salt sensitivity was defined as a significant drop in mean arterial pressure (> 3 mm Hg, mean of 60 readings taken on the seventh day of each diet, P < .05) during the low-salt diet. On the fifth and seventh days of each week, subjects were given an oral load of either sodium citrate (0.7 mmol/kg) or ammonium chloride (2.2 mmol/kg), respectively, in a randomized order, and arterial and urinary acid-base status was assessed at baseline and followed for 8 hours thereafter. According to the above definition, 13 subjects were considered salt sensitive. During the high-salt diet, mean arterial pressure was higher in the salt-sensitive than in the salt-resistant group (P < .01). Cumulative urinary bicarbonate excretion after the administration of sodium citrate was lower in the salt-sensitive than in the salt-resistant subjects during both the low-salt (46%, P < .001) and high-salt (32%, P < .01) diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular basis of human salt sensitivity: the role of the 11beta-hydroxysteroid dehydrogenase type 2.

Salt-sensitive subjects (SS) increase their blood pressure with increasing salt intake. Because steroid hormones modulate renal sodium retention, we hypothesize that the activity of the 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) enzyme is impaired in SS subjects as compared with salt-resistant (SR) subjects. The 11betaHSD2 enzyme inactivates 11-hydroxy steroids in the kidney, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids. We performed an association study using a recently identified single AluI polymorphism in exon 3 and a polymorphic microsatellite marker of the HSD11B2 gene in 149 normotensive white males (37 SS and 112 SR). The activity of the enzyme 11betaHSD2 was assessed by determining the urinary ratio of cortisol (THF+5alphaTHF) to cortisone (THE) metabolites by gas chromatography in all the 37 SS subjects and in 37 age- and body habitus-matched SR volunteers. Mean (THF+5alphaTHF)/THE ratio was markedly elevated in SS subjects compared with SR subjects (1.51 +/- 0.34 vs. 1.08 +/- 0.26, P < 0.00001), indicating enhanced access of glucocorticoids to the mineralocorticoid receptor in SS subjects. In 58% of SS subjects this ratio was higher than the maximum levels in SR subjects. The salt-induced elevation in arterial pressure increased with increasing (THF+5alphaTHF)/THE ratio (r2 = 0.51, P < 0.0001). A total of 12 alleles of the polymorphic microsatellite marker were detected. Homozygosity for the allele A7 was higher in SS subjects than in SR subjects (41 vs. 28%, P < 0.005), whereas the occurrence of the allele A7 with allele A8 was lower in SS subjects than in SR subjects (8 vs. 15%, P < 0.03). The prevalence of salt sensitivity was 35% in subjects with allele A7/A7, whereas salt sensitivity was present in only 9% of the subjects with allele A7/A8. The (THF+5alphaTHF)/THE ratio was higher in subjects homozygous for the A7 microsatellite allele as compared with the corresponding control subjects. The prevalence of the AluI allele was 8.0% in SR subjects and 5.4% in SS subjects and did not correlate with blood pressure. The decreased activity of the 11betaHSD2 in SS subjects indicates that this enzyme is involved in salt-sensitive blood pressure response in humans. The association of a polymorphic microsatellite marker of the gene with a reduced 11betaHSD2 activity suggests that variants of the HSD 11B2 gene contribute to enhanced blood pressure response to salt in humans.

Effect of sodium chloride- and sodium bicarbonate-rich mineral water on blood pressure and metabolic parameters in elderly normotensive individuals: a randomized double-blind crossover trial.

OBJECTIVE: To examine the effect of sodium chloride- and sodium bicarbonate-rich mineral water on blood pressure and parameters of glucose and lipid metabolism in elderly normotensive individuals. METHODS: We examined 21 healthy men and women aged 60-72 years in a randomized, placebo-controlled, double-blind crossover trial. After reducing dietary salt intake to below 100 mmol/day, study participants were randomly assigned to drink 1.5 l daily of a sodium chloride-rich (sodium 84.5 mmol/l, chloride 63.7 mmol/l, bicarbonate 21.9 mmol/l), a sodium bicarbonate-rich (sodium 39.3 mmol/l, chloride 6.5 mmol/l, bicarbonate 48.8 mmol/l) and a low-sodium (placebo: sodium, chloride and bicarbonate < 0.02 mmol/l) mineral water for 4 weeks each in a three-phase crossover order. Each phase was separated by a 2-week washout period in which the study participants remained on a low-salt diet. Compliance was assessed by biweekly urinary electrolyte excretion and five study participants were excluded from analysis for failing to complete the trial or to fulfil the compliance criteria. RESULTS: Mean arterial blood pressure was significantly lower during the periods of consuming low-sodium -7.0 +/- 7.2 mmHg, P < 0.001) or sodium bicarbonate-rich (-5.7 +/- 6.4 mmHg, P < 0.05) water than at baseline. In contrast, blood pressure during the phase of drinking sodium chloride-rich water was identical to that at baseline. Ambulatory 24 h blood pressure, oral glucose tolerance and plasma lipids were not affected by the different regimens. Urinary calcium excretion was significantly reduced by drinking low-sodium or sodium bicarbonate-rich water but was unchanged under the sodium chloride-rich water. CONCLUSION: Consumption of sodium chloride-rich mineral water can abolish the blood pressure reduction induced by dietary salt restriction in elderly individuals. Sodium bicarbonate-rich mineral water in conjunction with a low-salt diet may have a beneficial effect on calcium homeostasis.

Relationship between ambulatory and resting blood pressure responses to dietary salt restriction in normotensive men.

OBJECTIVE: To examine the relationship between changes in resting and ambulatory blood pressures induced by dietary salt restriction in 90 young normotensive men. METHODS: Subjects were given a standardized low-salt diet containing 20 mmol sodium chloride per day for 14 days. To this diet, a daily supplement of 20 tablets of slow sodium (10 mmol NaCl per tablet) or placebo was added in a randomized single-blind cross-over fashion for 7 days. The ambulatory blood pressure was measured on the sixth day and the resting blood pressure was measured on the seventh day of each dietary period. RESULTS: Although salt intake did not affect blood pressure levels in the whole group, the response of the blood pressure was quite variable among individual subjects. Salt-induced changes in resting systolic (r = 0.30, P = 0.006) and mean (r = 0.27, P = 0.014) blood pressures, but not diastolic blood pressure, were correlated positively to changes in daytime ambulatory blood pressure. The changes in resting systolic and mean blood pressures were also correlated significantly to the nocturnal falls in systolic (r = 0.26, P = 0.015) and mean (r = 0.27, P = 0.012) blood pressure levels and heart rate (r = 0.26, P= 0.015) under the high-salt diet. Diet-induced changes in resting mean blood pressure were correlated significantly to the daytime ambulatory blood pressure (r = 0.30, P < 0.005) and the resting heart rate (r = 0.24, P < 0.02) under the high-salt diet. CONCLUSION: Salt-induced changes in resting blood pressure in young normotensive men are correlated positively to changes in ambulatory daytime blood pressure levels as well as to the daytime ambulatory blood pressure and the nocturnal fall in blood pressure under a high-salt diet. These findings suggest that dietary salt-intake restriction can lower both resting and daytime ambulatory blood pressure levels in some normotensive individuals who may be predisposed to the development of hypertension.

Relationship between angiotensinogen, leptin and blood pressure levels in young normotensive men.

BACKGROUND AND AIMS: Although the relationship between an increase in adipose tissue and a rise in blood pressure has long been recognized, the mechanism linking these two phenomena has yet to be fully understood. Recently, it has become evident that adipose tissue is a rich source of metabolically active molecules, including free fatty acids, leptin and angiotensinogen, the precursor of angiotensin II. The latter finding has prompted speculation on the possible role of adipocyte-derived angiotensinogen in the relationship between body weight and blood pressure. Therefore we examined the relationship between blood pressure, angiotensinogen, body mass index (BMI) and leptin levels in healthy normotensive subjects who are genetically predisposed to the development of hypertension. SUBJECTS AND METHODS: We studied 40 subjects with a positive family history of hypertension and 51 subjects with a negative family history. After the blood pressure measurements, blood samples were collected for the assessment of angiotensinogen, leptin, glucose, insulin, renin activity and electrolytes. Oral glucose tolerance was studied by an oral glucose tolerance test (75 g glucose). RESULTS: Plasma angiotensinogen was significantly correlated with both BMI (r=0.29, P < 0.01) and plasma leptin (r=0.40, P < 0.001). While plasma angiotensinogen and blood pressure were positively correlated only in subjects with a positive family history of hypertension (r=0.33, P< 0.05), plasma leptin was related to blood pressure in both groups (r=0.26, P=0.01). Furthermore, the insulin response to an oral glucose load was significantly related to both plasma angiotensinogen (r=0.22, P< 0.05) and plasma leptin (r=0.47, P< 0.001). CONCLUSIONS: These findings support the hypothesis that circulating angiotensinogen levels are related to adipose mass in young, normotensive, nonobese men. Further studies on the relationship between adipose tissue and systemic or local renin-angiotensin systems appear warranted.

G-protein beta3 subunit 825T allele and response to dietary salt in normotensive men.

BACKGROUND AND AIMS: A functional single-nucleotide variant of the gene encoding the beta3 subunit of heterotrimeric G proteins (Gbeta3 C825T), associated with enhanced G-protein activation and increased activity of the sodium-proton exchanger (NHE1), has been implicated in the development of hypertension. Given the possible involvement of NHE1 in sodium homeostasis, we tested the hypothesis that the Gbeta3 825T allele determines the response of the renin-angiotensin system and blood pressure to dietary salt restriction. METHODS: Young normotensive men (20-30 years old, n = 193) were recruited within the framework of the Berlin Salt-Sensitivity Trial and studied on low- (20 mmol/day) and high-salt (220 mmol/day) dietary protocols. Subjects were characterized for parameters of the renin-angiotensin system and blood pressure response and genotyped for the Gbeta3 C825T polymorphism. RESULTS: The genotype distribution was in Hardy-Weinberg equilibrium (CC = 90, CT = 81 and TT = 22). The responses of the renin-angiotensin system and blood pressure to the dietary protocol were virtually identical between the genotypic groups. Furthermore, when subjects were classified as salt-resistant (n = 145) or salt-sensitive (n = 48), genotype distribution was comparable between the two groups (salt-resistant: TT = 17, CT = 60, CC = 68, qT = 0.32; salt-sensitive: TT = 5, CT = 21, CC = 22, qT = 0.32). CONCLUSION: These findings do not support the hypothesis that the Gbeta3 C825T polymorphism determines the response of the renin-angiotensin system to salt depletion or can serve as an early genetic marker of salt sensitivity in young normotensive men.

Effect of dietary salt restriction on urinary serotonin and 5-hydroxyindoleacetic acid excretion in man.

OBJECTIVE: To determine the effect of dietary salt restriction on urinary excretion of serotonin and its principal metabolite 5-hydroxyindoleacetic acid (5-HIAA) in man. DESIGN: We studied 16 healthy male volunteers (age range 20-28 years) who ate a standard diet containing 20 mmol/day NaCl, to which either 220 mmol/day NaCl or placebo was added as a supplement for 1 week each, according to a randomized, single-blind crossover design. METHODS: Urinary excretion of serotonin, 5-HIAA, noradrenaline and vanillylmandelic acid (VMA) were measured during the low- and high-salt periods using reverse-phase high-performance liquid chromatography. RESULTS: During the low-salt diet, 24-h urinary excretion of serotonin increased by 42%, accompanied by a 52% rise in the excretion of 5-HIAA. Salt restriction also increased noradrenaline excretion by 77% and VMA excretion by 40%. Regression analysis revealed a strong positive relationship between the excretion of serotonin and of noradrenaline (r = 0.84, P < 0.001) and between that of 5-HIAA and of VMA (r = 0.74, P < 0.001). CONCLUSIONS: Salt restriction stimulates the serotonergic system in man. Stimulation of this system, in conjunction with the sympathetic nervous system, may contribute to renal sodium conservation during dietary salt restriction in man.

Angiotensinogen M235T variant and salt sensitivity in young normotensive Caucasians.

BACKGROUND AND AIMS: A single-nucleotide variant of the angiotensinogen gene (AGT 235T) has been associated with essential hypertension and increased plasma levels of angiotensinogen. This variant may also serve as a genetic marker for the increased blood pressure response to dietary salt intake, but the relationship between AGT genotype and salt sensitivity has not been studied until now. We therefore examined the relationship between the AGT 235T genotype and the blood pressure response to short-term dietary salt restriction in young normotensive men. SUBJECTS AND METHODS: A total of 187 young normotensive men were characterized for family history of hypertension, salt sensitivity, plasma parameters of the renin-angiotensin system under high- and low-salt diets, and the AGT 235T genotype. RESULTS: While the T allele was significantly associated with a positive family history of hypertension (chi2 = 7.0; P< 0.03) and higher plasma angiotensinogen levels (P< 0.015) and renin activity (P < 0.037), blood pressure under both diets was not significantly affected by the AGT genotype. When the subjects were classified into salt-resistant and salt-sensitive groups, genotypic distribution was nearly identical between both groups (frequency of T allele: 0.45 versus 0.46). CONCLUSION: Our findings demonstrate that the AGT 235T allele is significantly associated with a positive family history of hypertension, but is not an important determinant of the blood pressure response to dietary salt intake in young normotensive subjects. It is therefore unlikely that the AGT 235T genotype can serve as an early genetic marker of salt sensitivity.

Psychophysiological reactivity of salt-sensitive normotensive subjects.

OBJECTIVE: To evaluate the psychophysiological response to mental stress of young healthy salt-sensitive normotensive subjects. METHODS: Thirty-two healthy volunteers who had previously been phenotyped for salt sensitivity were selected for the study. The 16 salt-sensitive and 16 salt-resistant subjects, who were matched for age, body mass index and family history of hypertension, underwent a mental stress test consisting of an information-processing task performed under time pressure (the Manometer test). During the experimental session the blood pressure, heart rate and pulse-wave velocity were registered continuously. Before and after the mental task subjects were instructed to complete several standardized psychological state and trait questionnaires. RESULTS: Mental stress resulted in a greater rise in blood pressure (P < 0.05) and in pulse-wave velocity (P < 0.01) in salt-sensitive than in salt-resistant individuals. Salt-sensitive subjects also displayed significantly higher levels of anxiety (P < 0.01) and a lower level of control of anger (P < 0.01) than did salt-resistant subjects. Furthermore, the level of irritation of the salt-sensitive subjects was higher both before (P < 0.01) and after (P < 0.05) the stress test CONCLUSIONS: An increased responsiveness of the blood pressure to mental stress and an increased level of irritation are associated with salt sensitivity in normotensive subjects. These findings are in line with the hypothesis that psychophysiological traits play a role in the development of salt-sensitive hypertension.

Hpa II polymorphism of the atrial natriuretic peptide gene and the blood pressure response to salt intake in normotensive men.

OBJECTIVE: To test the hypothesis that the Hpa II variant of the atrial natriuretic peptide gene (ANP), which has been reported to be more common among black hypertensives than it is among normotensive controls, is related to the response of blood pressure to salt intake in normotensive Caucasians. METHODS: One hundred and three young (aged 19-35 years) male volunteers were fed a low-salt diet (20 mmol NaCl/day) for 2 weeks and a supplement of either 200 mmol NaCl/day (slow sodium) or placebo for 1 week each in a randomized double-blind cross-over order. Salt sensitivity was defined as a significant (P < 0.05) decrease in resting mean arterial blood pressure by > 3 mmHg under the low-salt diet. The genotype was determined by amplification of genomic DNA extracted from peripheral leukocytes and subsequent digestion of the amplicon with Hpa II restriction enzyme. RESULTS: According to the above definition, 27 subjects were salt sensitive. There were no significant differences in age, body-mass index and waist:hip ratio between the salt-sensitive and salt-resistant groups. Only salt-sensitive subjects displayed a significantly higher blood pressure under the high-salt diet (increase in mean arterial pressure 5.6 +/- 2.4 mmHg, P < 0.001). The prevalence of the ANP-Hpa II wild-type (w) allele did not differ between the salt-sensitive (qw = 1.0, qm = 0) and the salt-resistant group (qw = 0.96, qm = 0.04). Furthermore, the salt-induced response of blood pressure did not differ between homozygotes (ww) and heterozygotes (wm). CONCLUSIONS: Our findings do not support the hypothesis that the ANP-Hpa II polymorphism is a marker for salt sensitivity in young Caucasian normotensives.

Aldosterone synthase gene (CYP11B2) C-344T polymorphism in Caucasians from the Berlin Salt-Sensitivity Trial (BeSST).

OBJECTIVE: Aldosterone synthase (CYP11B2) is a key enzyme in the biosynthesis of aldosterone. Recently, the T allele of a polymorphism in the 5'-flanking region of the CYP11B2 gene (C-344T) has been reported to be more frequent in hypertensives than in normotensives, and has also been associated with increased plasma aldosterone levels. We therefore hypothesized that this variant may be related to increased blood-pressure response to dietary salt intake. SUBJECTS AND METHODS: We genotyped 1 63 young normotensive men recruited within the framework of the Berlin Salt-Sensitivity Trial (BeSST) for the CYP11B2 C-344T polymorphism. Subjects were characterized for family history of hypertension, plasma parameters of the renin-angiotensin-aldosterone system and blood-pressure response to a high (220 mmol/day) and low (20 mmol/day) salt diet RESULTS: The frequency of the -344T allele (0.45) was similar to that reported previously and genotype distribution was in Hardy-Weinberg equilibrium (CC, n = 55; CT, n = 71; TT, n = 37). There was a trend towards a higher frequency of the T allele in subjects with a positive family history of hypertension (0.48 versus 0.42), but the C-344T genotype was not related to blood pressure under either diet Furthermore, when subjects were classified into salt-sensitive and salt-resistant groups, allelic distribution did not differ between the two groups (qT = 0.43 versus qT = 0.45). While renin activity and plasma aldosterone levels were not related to genotype, plasma angiotensinogen was significantly higher in T-allele carriers under both the high (P = 0.02) and low (P = 0.008) salt diet. CONCLUSION: Our findings do not support the hypothesis that the C-344T polymorphism of the CYP11B2 gene is associated with salt sensitivity or increased activity of the renin-angiotensin system in young normotensive subjects. It is, therefore, unlikely that the C-344T polymorphism is a genetic marker for salt sensitivity in young normotensive Caucasian men.

Dietary v intravenous salt loading for the assessment of salt sensitivity in normotensive men.

The purpose of this study was to compare the blood pressure response to two commonly used protocols for the assessment of salt sensitivity in normotensive men, involving either the rapid intravenous administration of a saline load followed by diuretic-induced salt depletion, or the more physiologic but time-consuming approach involving dietary salt depletion and repletion. Twenty-two healthy male volunteers (22-35 years old) were given a saline load (2 L of 0.9% NaCl over 4 h, i.v.), and on the following day, a low-salt diet (20 mmol NaCl) and furosemide (3 x 40 mg, po). Resting mean arterial blood pressure (MABP) was assessed after the saline load and on the morning following salt depletion. After a 2-week wash-out period, subjects were given a low-salt diet (20 mmol/day NaCl) for 2 weeks, supplemented by either 220 mmol/day NaCl or placebo for 1 week each. At the end of each week, resting MABP was assessed in the supine subjects. Although MABP changes were quite variable (iv, mean -2.1 mm Hg; range, -9.1 to +5.6; diet, mean -2.0 mm Hg; range, -14.3 to +7.2), there was a significant correlation between the salt-induced changes in MABP (r = 0.56, P < .01) and diastolic blood pressure (r = 0.56, P < .01) between the two protocols. However, in individual subjects, blood pressure response to the intravenous protocol did not uniformly predict the blood pressure response to the dietary protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of sodium salts on plasma renin activity and norepinephrine response to orthostasis in salt-sensitive normotensive subjects.

The blood pressure-raising effect of sodium chloride in salt-sensitive individuals depends on the administration of both sodium and chloride. While sodium chloride is well known to suppress the activity of the renin-angiotensin-aldosterone and the sympathetic nervous system, the effects of nonchloride sodium salts on the response of these systems to physiological stimuli have not been previously studied. We therefore examined the effect of dietary intake of sodium chloride or sodium citrate on the activity of the renin-angiotensin-aldosterone and the sympathetic nervous system during rest and following stimulation by active orthostasis in normotensive salt-sensitive (n = 7) and salt-resistant (n = 8) subjects. The subjects were given a low-salt diet (20 mmol/day) for 3 weeks, to which a supplement of 200 mmol sodium per day, provided as either sodium chloride or sodium citrate, or a placebo, was added for 1 week each. We found that sodium chloride raised blood pressure in the salt-sensitive subjects (P < .005), while sodium citrate did not. Both salts, however, led to a similar suppression of the plasma levels of renin activity, angiotensin II, aldosterone, and norepinephrine (P < .01). Both sodium salts attenuated the renin response to orthostasis in salt-sensitive and salt-resistant individuals (P < .01), but the orthostasis-induced rise in renin activity was significantly smaller in the salt-sensitive than in the salt-resistant group under both sodium salts (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetic analysis of the thermic effect of food and its relationship to body composition in humans.

The course of energy expenditure after a meal can vary widely with regard to the slope of onset, amplitude, and duration of the thermic effect. The aim of the present study was to explore the relationship between the thermic effect of food (TEF), as characterized by kinetic analysis of postprandial energy expenditure, body composition, and variables related to the metabolic syndrome including central obesity, hypertension, and glucose tolerance. A total of 181 men and women (body mass index [BMI] range, 19.4 to 52.2 kg/m2) were characterized for body composition, blood pressure, oral glucose tolerance, and energy expenditure after a test meal. Energy expenditure, as measured by indirect calorimetry, was analyzed over a 6-hour period by 3-parameter curve fitting using equations derived from kinetics describing a biphasic reaction involving 2 consecutive first-order reactions (A-->B-->C). Apart from total thermic effect of food (TEFk), the curve also provided an estimate of time of peak (Tp) and amplitude of peak (Ap) for each subject. Multiple stepwise regression analysis with TEFk, Ap, and Tp as dependent variables showed significant effects of sex, age, body weight, body fat, beta-blockade, and body composition on TEF curve parameters. Cluster analysis based on Tp shown 2 distinct clusters with significant differences in age and body fat mass. This study shows that kinetic analysis of postprandial energy expenditure can be used to examine the determinants of the time course of the thermic effect of food in man.

Salt intake and hypertension in renal transplant patients.

BACKGROUND: Dietary salt restriction is currently widely recommended as an important non-pharmacological measure for the treatment of hypertension. However, the relationship between dietary salt intake and post-transplant hypertension has not been extensively investigated. PATIENTS AND METHODS: We examined the relationship between dietary salt intake and the prevalence of hypertension in 129 renal transplant patients with stable allograft function (serum creatinine < 400 micromol/l, variation in serum creatinine during the preceding two months < 20%). Salt intake was assessed by measuring 24-hour urinary excretion of sodium on an unrestricted diet. Hypertension was defined based on the prescription of antihypertensive medication, and the number of antihypertensive drugs was considered a surrogate marker for severity of hypertension. Patients were divided into tertiles based on urinary sodium excretion and analyzed by chi2-testing. RESULTS: The prevalence of hypertension was 74% and the mean sodium excretion was 178 mmol/d (range: 56 to 603). There was no statistical difference in the frequency of antihypertensive medication between patients with low (76%, UNa = 107 mmol/d), medium (73%, UNa = 178 mmol/d), or high sodium (73%, UNa = 272 mmol/d) excretion. Furthermore, the number of antihypertensive drugs (in treated patients) was similar between the tertiles. There was also no correlation between urinary sodium excretion and systolic (r = -0.05) or diastolic (r = 0.08) blood pressure levels. CONCLUSION: We conclude that dietary salt intake in transplant patients with stable allograft function is higher than currently recommended. There is, however, no relationship between salt intake and the prevalence of hypertension in these patients. These data do not support the hypothesis that the prevalence or severity of post-transplant hypertension is markedly affected by dietary salt intake.