Neurohormonal and metabolic effects of severe and moderate salt restriction in non-obese normotensive adults. Effects of sodium salts on plasma renin activity and norepinephrine response to orthostasis in salt-sensitive normotensive subjects. Sodium sensitivity in essential hypertension: role of the renin-angiotensin-aldosterone system and predictive value of an intravenous frusemide test. Divergent hemodynamic and hormonal responses to varying salt intake in normotensive subjects. Effects of moderate sodium restriction on clinic and twenty-four-hour ambulatory blood pressure in elderly hypertensive subjects. Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial. Normal renal tubular response to changes of sodium intake in hypertensive man. Normal responses of atrial natriuretic factor and renal tubular function to sodium loading in hypertension-prone humans. Metabolic and orthostatic blood pressure responses to a low-sodium diet in elderly hypertensives.
The effects of severe and moderate sodium restriction on blood pressure, neurohormonal activity and serum lipids were studied in non-obese normotensive adults.
                In the first part of the study, 163 subjects were randomly assigned to a diet of 20 or 300 mmol/day sodium for 1 week each. In the second part, 25 subjects were given a diet of 85 or 200 mmol/day sodium for 4 weeks each in random order.
                After severe salt restriction 19% of the subjects had a significant decline (salt-sensitive group), 15% showed a significant rise (counter-regulator group) and 66% exhibited no change in blood pressure (salt-resistant group). Severe sodium restriction increased plasma renin activity and noradrenaline concentration, as well as serum total and low-density lipoprotein-cholesterol and triglycerides. After correction for haematocrit, only the changes in total and low-density lipoprotein-cholesterol remained significant. The rise in plasma renin activity during salt restriction was steeper in the counter-regulator group than in the other groups, whereas the changes in plasma noradrenaline concentrations were similar in all groups. During moderate salt restriction, plasma renin activity and noradrenaline concentration were significantly increased, but serum lipid concentrations and blood pressure did not change.
                In non-obese normotensive adults, severe and moderate salt restriction stimulates neurohormonal activity. In contrast to severe salt restriction, a moderate reduction in dietary salt intake does not influence blood lipids in 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) In order to determine factors contributing to sodium induced changes of blood pressure, 20 patients with essential hypertension were studied when on their regular sodium intake and after two weeks of a low sodium diet (50 mmol daily) and two weeks of a high sodium diet (300 mmol daily). There were two periods of regular sodium intake, one of four weeks at the beginning and one of two weeks at the end of the study. The change in mean arterial pressure between the high and low salt diets (delta MAP) was regarded as a measure of sodium sensitivity, and was directly correlated with age and initial blood pressure. Compared with non-responders, responders (delta MAP 10 mmHg or more) showed a lesser activation of the renin-angiotensin-aldosterone system during the low salt period. The response to the administration of intravenous frusemide was not helpful in predicting sodium sensitivity. A significant but relatively small (4.2 mmHg) reduction in MAP was obtained during low salt period compared with the first period of regular sodium intake. The data suggest that moderate dietary sodium restriction can help to reduce the blood pressure of the relatively older patient with hypertension. Blood pressure responses to 1 week of low-salt (20 mmol sodium/d) and high-salt (300 mmol sodium/d) intake were investigated in a single-blind randomized study in 163 white, nonobese normotensive subjects (65 women and 98 men; mean age, 38 +/- 1.2 years). The individuals were classified as salt sensitive when mean arterial blood pressure rose by at least 5 mm Hg during high-salt intake, as salt resistant when mean arterial blood pressure changed by less than 5 mm Hg, and as "counterregulator" when mean arterial blood pressure fell by at least 5 mm Hg during the high-salt diet. Reexamination of 31 subjects showed that this approach to the testing of salt sensitivity was reliable and reproducible. Thirty subjects (18.4%) were classified as salt sensitive, 108 (66.3%) as salt resistant, and 25 (15.3%) as counterregulators. Multiple regression analysis revealed that age, body weight, and family history of hypertension contributed significantly to the change in blood pressure after the diets. Salt sensitivity was more frequent in older subjects and in those with a positive family history of hypertension. An increase in blood pressure after salt restriction was more likely in younger individuals and in those with a negative family history of hypertension. Plasma renin activity and plasma aldosterone concentrations were lower in salt-sensitive compared with salt-resistant and counterregulating subjects. The rise in plasma renin activity during salt restriction was most pronounced in counterregulating subjects. Plasma norepinephrine concentrations were not different among the groups.(ABSTRACT TRUNCATED AT 250 WORDS) To assess the effects of 80 mmol/day reduction in dietary sodium intake on clinic and 24-h ambulatory blood pressure in elderly hypertensive subjects.
                Double-blind, randomized, placebo-controlled, crossover trial lasting 10 weeks, following a 4-week run-in period.
                Seventeen untreated subjects with essential hypertension [systolic blood pressure (SBP) > or = 160 mmHg and/or diastolic blood pressure (DBP) > or = 95 mmHg], mean age 73 years (range 66-79).
                Subjects had clinic blood pressure and 24-h urinary electrolyte excretion measured while on their normal diet. Following a 4-week run-in period on a reduced-sodium diet (80-100 mmol/24 h) subjects entered a 10-week crossover trial of 80 mmol/24 h sodium supplement or matching placebo while continuing on the reduced-sodium diet.
                The within-patient change in clinic and 24-h ambulatory blood pressures at the end of each intervention period.
                Mean urinary sodium excretion at the end of the run-in phase rose during the high sodium intake phase and was reduced significantly at the end of the low sodium intake phase. There was a significant reduction in clinic supine SBP between the high- and low-sodium phases. There was no significant change in standing SBP, supine or standing DBP or pulse rate between phases. There was a non-significant reduction in mean 24-h SBP and DBP on the low sodium intake. At the end of the low-sodium phase there was a significant increase in plasma renin activity and aldosterone levels, but no change in plasma electrolytes.
                Overall, moderate sodium restriction in elderly hypertensives resulted in a significant fall in clinic supine SBP only, although marked differences in intersubject responses were found. Moderate sodium restriction may be of benefit in only some elderly hypertensive subjects as part of a non-pharmacological regimen for blood pressure reduction. Observational studies indicate a significant relation between dietary sodium and level of blood pressure. However, the role of salt sensitivity in the development of resistant hypertension is unknown. The present study examined the effects of dietary salt restriction on office and 24-hour ambulatory blood pressure in subjects with resistant hypertension. Twelve subjects with resistant hypertension entered into a randomized crossover evaluation of low (50 mmol/24 hours x 7 days) and high sodium diets (250 mmol/24 hours x 7 days) separated by a 2-week washout period. Brain natriuretic peptide; plasma renin activity; 24-hour urinary aldosterone, sodium, and potassium; 24-hour ambulatory blood pressure monitoring; aortic pulse wave velocity; and augmentation index were compared between dietary treatment periods. At baseline, subjects were on an average of 3.4+/-0.5 antihypertensive medications with a mean office BP of 145.8+/-10.8/83.9+/-11.2 mm Hg. Mean urinary sodium excretion was 46.1+/-26.8 versus 252.2+/-64.6 mmol/24 hours during low- versus high-salt intake. Low- compared to high-salt diet decreased office systolic and diastolic blood pressure by 22.7 and 9.1 mm Hg, respectively. Plasma renin activity increased whereas brain natriuretic peptide and creatinine clearance decreased during low-salt intake, indicative of intravascular volume reduction. These results indicate that excessive dietary sodium ingestion contributes importantly to resistance to antihypertensive treatment. Strategies to substantially reduce dietary salt intake should be part of the overall treatment of resistant hypertension. In a comparative study the influence of changes in dietary sodium intake on blood pressure, renal function, extracellular fluid volume, the renin-angiotensin-aldosterone system and plasma concentrations of arginine vasopressin, atrial natriuretic factor and cyclic guanosine monophosphate (GMP) was investigated in 12 patients with essential hypertension and in 10 normotensive controls. The subjects were studied after 4 days on a low (50 mmol/day), medium (180 mmol/day) or high (380 mmol/day) sodium intake. Renal sodium handling was assessed by simultaneous measurements of 51Cr-ethylenediaminetetraacetic acid (EDTA), lithium and sodium clearances. Identical values for the extracellular fluid volume, glomerular filtration rate and proximal and distal tubular resorption rates of sodium and water were found in the hypertensive patients and the controls at all three levels of sodium intake. In both groups, raising the sodium intake from low to high significantly increased 51Cr-EDTA and lithium clearance (an indirect measure of end-proximal fluid delivery), with intermediate values for the medium-sodium diet. The estimated values of fractional proximal and distal sodium resorption decreased when sodium intake was raised; the absolute proximal sodium resorption rate did not change, whereas the absolute distal sodium resorption rate as well as the extracellular fluid volume and sodium clearance increased. Blood pressure and the heart rate were unaffected by sodium intake. In both hypertensives and controls, plasma concentrations of active renin, angiotensin II and aldosterone decreased with increasing sodium intake, arginine vasopressin did not change, and atrial natriuretic factor and cyclic GMP increased.(ABSTRACT TRUNCATED AT 250 WORDS) In order to explore the hypothesis of an atrial natriuretic factor (ANF) deficiency in prehypertension, we compared the response to sodium loading on ANF and renal function in subjects with positive and negative histories of hypertension.
                Twenty-two offspring of hypertensive parents (OH) and 20 offspring of normotensive parents (ON) were studied after 4 days of low (50 mmol/day) or high (300 mmol/day) dietary sodium intake. The diets were allocated randomly. Blood pressure (BP), renal function, plasma concentration of ANF, cyclic guanosine monophosphate (cGMP), renin, angiotensin I and II, aldosterone, endothelin and catecholamines were determined during a clearance period of 90 min on both diets. Neurohormones were measured by radioimmunoassays. Renal function was determined by simultaneous measurements of 51Cr-ethylenediaminetetraacetate (a marker of glomerular filtration rate), lithium and sodium clearances.
                Supine systolic and diastolic BPs were significantly elevated in OH, with both low and high dietary sodium intake. There was no difference in ANF and cGMP concentrations on the low sodium diet. Increasing sodium intake caused a similar increase in ANF in OH and ON but cGMP did not change significantly. As expected the activity of the renin-angiotensin-aldosterone system was decreased by enhancing sodium intake but with both low and high sodium intake plasma renin concentration was significantly higher in OH than in ON. Activation of the sympathetic nervous system with low sodium intake was indicated by a moderate increase in plasma concentrations of epinephrine and norepinephrine in both groups. The renal effects were characterized by significant increases in GFR, lithium and sodium clearances with increasing sodium intake. There were no differences between OH and ON. Estimated values of fractional proximal and distal tubular sodium reabsorption decreased significantly and in a similar way in both OH and ON.
                These results indicate that the renal and neuroendocrine responses to dietary sodium loading are similar in both OH and ON. The only difference was a higher BP and an elevated plasma renin concentration on both dietary regimens in OH compared with ON. In particular, in OH and ON an identical increase in plasma ANF concentration in response to sodium loading was found. Thus, this study cannot support the hypothesis of a dysregulation of ANF in hypertension-prone humans. In view of the concern regarding the potential risks and benefits of sodium restriction, the effect on biochemical and orthostatic responses from a moderate reduction in sodium intake in elderly persons that is sufficient to lower systolic blood pressure (SBP) was examined. Seventeen hypertensive subjects aged 65-79 years entered a double-blind randomized placebo controlled cross-over trial of a low sodium diet plus placebo tablets vs a low sodium diet plus sodium tablets (80 mmols/day) each for 5 weeks. At the end of high and low sodium periods, two 24-h urine collections and venous blood samples were undertaken and supine and standing BPs were recorded. On the low compared to the high sodium phase (urinary sodium excretion 95 +/- 36 vs 174 +/- 40 mmols/24-h, respectively), clinic supine SBP fell by 8 mm Hg (95% CI: 1-15 mm Hg, P< 0.05) and diastolic BP (DBP) by 1 mm Hg (CI: -3 to 5 mm Hg); there was no change in total LDL- and HDL-cholesterol and triglyceride levels, serum calcium, phosphate, parathyroid hormone, glucose, creatinine clearance or urinary albumin excretion rate. Serum urate was significantly higher during the low compared to high sodium intake (304 +/- 56 vs 277 +/- 44 micromols/l). Orthostatic BP responses during the high and low sodium intakes were unchanged. In summary, after 5 weeks of moderate sodium restriction no adverse effects other than an increase in serum urate was seen in elderly hypertensive persons.
Sodium reduction resulted in a 1% decrease in blood pressure in normotensives, a 3.5% decrease in hypertensives, a significant increase in plasma renin, plasma aldosterone, plasma adrenaline and plasma noradrenaline, a 2.5% increase in cholesterol, and a 7% increase in triglyceride. In general, these effects were stable in studies lasting for 2 weeks or more.