Reduction In Urinary Sodium Excretion Research Articles

Changes in blood pressure during treatment with the tyrosine kinase inhibitor lenvatinib.

BackgroundWithin the class of tyrosine kinase inhibitors (TKIs), which are used for the treatment of numerous advanced cancers, lenvatinib is associated with a higher prevalence of hypertension (HT) compared with other TKIs. In this study, we investigated the effect of lenvatinib on blood pressure (BP) and associated factors.MethodsThis single-centre, retrospective observational study included 25 consecutive patients treated with lenvatinib for unresectable hepatocellular carcinoma from April 2018 to December 2018 at the study institution. We assessed changes in BP using ambulatory BP monitoring, urinary sodium excretion, kidney function, use of antihypertensive agents and diuretics, and fluid retention following treatment initiation with lenvatinib.ResultsAt 1 week after treatment initiation, the mean BP and the percentage of patients with riser pattern significantly increased compared with those at the baseline. Although there were no significant changes at 1 week, urinary sodium excretion (153.4 ± 51.7 and 112.5 ± 65.0 mEq/day at 1 and 3 weeks, respectively, P < 0.05) and estimated glomerular filtration rate significantly decreased and the number of patients with fluid retention increased at 3 weeks. Furthermore, patients with fluid retention had significantly higher BP or required more intensive BP treatment compared with those without fluid retention.ConclusionsLenvatinib might lead to HT without fluid retention soon after the initiation of treatment, subsequently leading to a reduction in urinary sodium excretion, thereby contributing to a rise in BP by fluid retention.

Urine 24-Hour Sodium Excretion Decreased between 1953 and 2014 in Japan, but Estimated Intake Still Exceeds the WHO Recommendation

Background: Accurate monitoring of sodium intake is necessary for evaluating strategies used to reduce sodium intake. However, no repeat survey has been conducted in representative populations in Japan to examine trends in sodium intake with the use of 24-h urinary sodium excretion, a standard evaluation method for sodium intake monitoring.Objective: The objective of this study was to examine potential trends in sodium intake by examining previous reports of 24-h urinary sodium excretion in healthy Japanese adult populations.Methods: We systematically searched for reports of 24-h urinary sodium excretion in healthy Japanese adult populations (mean age range: 18-69 y). We searched PubMed and Web of Science for English-language articles and hand-searched 7 Japanese scientific journals for Japanese-language articles. Trends in urinary sodium excretion were examined with the use of weighted linear regression and random-effects meta-regression analyses, with adjustment or stratification to address study characteristics (population mean age, percentage of men, and sample size) and study assessment for completeness of urine collection.Results: We identified 68 reports of urinary sodium excretion from 53 articles published from 1953 through 2014 that showed high rates of urinary sodium excretion in healthy Japanese adult populations (weighted mean: 4900 mg/d). The rate of urinary sodium excretion significantly decreased between 1953 and 2014, by 4350 mg/d (P < 0.001); however, the rate of reduction in urinary sodium excretion was variable and decreased with time (P-linear trend <0.001 and P-quadratic trend <0.001). In the random-effects meta-regression analysis of studies that assessed completeness of urine collection with creatinine excretion, no significant relation between urinary sodium excretion and year was observed from 1978 to 2014 (β = -16, P = 0.40).Conclusion: Despite a decrease in urinary sodium excretion in healthy Japanese adult populations between 1953 and 2014, sodium intake still exceeds the WHO recommendation for adults. This review was registered at PROSPERO as CRD42016035452.

OS 35-03 LEFT VENTRICULAR CHANGES ARE AFFECTED BY DIETARY SALT INTAKE IN PRIMARY ALDOSTERONISM

Objective: Primary aldosteronism is associated with increased left ventricular mass independent of blood pressure levels. Previous studies suggest that elevated aldosterone causes cardiac damage only in the presence of an inappropriate salt status. We examined the relevance of dietary salt intake on cardiac changes in patients with primary aldosteronism before and after treatment. Design and Method: Sixty-five patients with tumoral or idiopathic primary aldosteronism were recruited at a University medical center and followed after either surgical (n = 30) or medical (n = 35) treatment. At baseline and 1 year after treatment, cardiac morphological and functional variables were measured by echocardiography together with duplicate 24-h urinary sodium collections. Results: At baseline, significantly greater left ventricular mass index was associated with increasing urinary sodium and plasma aldosterone levels above the median of the distribution. During follow-up, blood pressure and left ventricular mass index decreased significantly with only mild and nonsignificant changes in left ventricular geometry and functional properties. At the end of follow-up, decrease in left ventricular mass index was significantly greater in patients who had more than 10% reduction in urinary sodium excretion than in the remaining patients. Changes in left ventricular mass induced by both surgical and medical treatment were directly and independently related with changes in blood pressure and urinary sodium excretion observed at the end of follow-up (Figure). Conclusions: In conclusion, these findings strongly support the hypothesis that dietary salt intake has a crucial role in aldosterone-related left ventricular changes and could contribute to cardiac damage in patients with primary aldosteronism.

Dietary Salt Intake Is a Determinant of Cardiac Changes After Treatment of Primary Aldosteronism

Primary aldosteronism is associated with increased left ventricular (LV) mass independently of blood pressure. Previous studies suggest that elevated aldosterone causes cardiac damage only in the presence of an inappropriate salt status. We examined the relevance of dietary salt intake on cardiac changes in patients with primary aldosteronism before and after treatment. Sixty-five patients with tumoral or idiopathic primary aldosteronism were recruited at a University medical center and followed after either surgical (n=30) or medical (n=35) treatment. At baseline and 1 year after treatment, cardiac morphology and functional variables were measured by echocardiography together with duplicate 24-hour urinary sodium collections. At baseline, LV mass index was associated with urinary sodium excretion and plasma aldosterone levels. During follow-up, blood pressure (from 167/102–135/83 mm Hg; P &lt;0.001) and LV mass index (from 50.5±13.0–44.4±8.9 g/m 2.7 ; P &lt;0.001) decreased significantly with nonsignificant changes in LV geometry and functional properties. At the end of follow-up, percentage decrease in LV mass index was significantly greater in patients who had &gt;10% reduction in urinary sodium excretion (15.0±12.5%) than in the remaining patients (5.5±9.3%; P &lt;0.001). Changes in LV mass index induced by both surgical and medical treatment were directly and independently correlated with changes in blood pressure (β=0.419; P =0.009) and urinary sodium excretion (β=0.334; P =0.012) observed at follow-up. These findings strongly support the hypothesis that dietary salt intake has a crucial role in aldosterone-related LV changes and could contribute to cardiac damage in patients with primary aldosteronism.

Systolic blood pressure reductions with sotagliflozin (LX4211), a dual SGLT1 and SGLT2 inhibitor, are associated with reductions in urinary sodium excretion

vs. V; N vs N+V). Table displays main results. All 3 treatments resulted in similar brachial and central systolic BP values. N alone or in combination with V resulted in lower 24-hour and daytime ACRPP values compared to V (by about 11-14%, p<0.001 each). This effect was driven largely by the heart-rate slowing effects of N; stroke work trended higher with N. Variability (standard deviation and coefficient of variation) of ACRPP and heart rate were lower with N and N/V than V. Results in African Americans, the majority subpopulation, were very similar to those of the entire treatment group. We conclude that the rate-slowing effects of nebivolol cause ambulatory cardiac workload to be lower for both N and N/V than V alone. Addition of V to N does not cause additional BP or rate-altering effects compared to N alone. Heart rate variability is also lower with N, either alone or in combination with V. These results were seen in African Americans.

Low-Sodium Dietary Approaches to Stop Hypertension Diet Reduces Blood Pressure, Arterial Stiffness, and Oxidative Stress in Hypertensive Heart Failure With Preserved Ejection Fraction

Recent studies suggest that oxidative stress and vascular dysfunction contribute to heart failure with preserved ejection fraction (HFPEF). In salt-sensitive HFPEF animal models, diets low in sodium and high in potassium, calcium, magnesium, and antioxidants attenuate oxidative stress and cardiovascular damage. We hypothesized that the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) would have similar effects in human hypertensive HFPEF. Thirteen patients with treated hypertension and compensated HFPEF consumed the DASH/SRD for 21 days (all food/most beverages provided). The DASH/SRD reduced clinic systolic (155–138 mm Hg; P =0.02) and diastolic blood pressure (79–72 mm Hg; P =0.04), 24-hour ambulatory systolic (130–123 mm Hg; P =0.02) and diastolic blood pressure (67–62 mm Hg; P =0.02), and carotid-femoral pulse wave velocity (12.4–11.0 m/s; P =0.03). Urinary F2-isoprostanes decreased by 31% (209–144 pmol/mmol Cr; P =0.02) despite increased urinary aldosterone excretion. The reduction in urinary F2-isoprostanes closely correlated with the reduction in urinary sodium excretion on the DASH/SRD. In this cohort of HFPEF patients with treated hypertension, the DASH/SRD reduced systemic blood pressure, arterial stiffness, and oxidative stress. These findings are characteristic of salt-sensitive hypertension, a phenotype present in many HFPEF animal models and suggest shared pathophysiological mechanisms linking these 2 conditions. Further dietary modification studies could provide insights into the development and progression of hypertensive HFPEF.

PS15 Policy Actions to Reduce Dietary Salt Intake: Price, Product, Place or Promotion? A Review of the Evidence

BackgroundA range of policies aim to reduce salt intake; however, their relative effects remain unclear. We undertook a narrative synthesis of existing evidence to determine the most promising approaches.MethodsWe searched...

The G Protein-Coupled Receptor Kinase 4 Gene Modulates Stress-Induced Sodium Excretion in Black Normotensive Adolescents

Approximately 20-40% of adolescents have shown a reduction of urinary sodium excretion (U(Na)V) in response to blood pressure (BP) increase during behavioral stress. G protein-coupled receptor kinase 4 (GRK4) mediates the pressure and natriuresis relation. The present study investigated the impact of GRK4 genetic variants on U(Na)V under stress. A total of 664 normotensive adolescents including whites and blacks (17.6 +/- 3.3 yrs, 43.4% blacks) were recruited. Participants were subjected to a stress-protocol including three 10-min tasks (a social competence interview, a virtual reality car driving simulation test, and a video game challenge), concluded by a urine collection. Three functional polymorphisms including R65L, A142V and A486V were genotyped. Given blacks compared with whites had significantly higher systolic BP (SBP) levels during rest (p < 0.001) and stress (p <or= 0.001), there was no statistical difference in U(Na)V in response to stress between the two ethnic groups. In blacks, compared with R65R homozygotes, individuals with R65L or L65L genotype had significantly lower levels of stress-induced U(Na)V (8.42 +/- 0.63 versus 9.85 +/- 0.37 mEq/h, p = 0.01). In summary, BP elevation seems uncoupled with U(Na)V increase during behavioral stress in black adolescents. The 65L allele of the GRK4 gene is associated with stress-induced U(Na)V reduction, suggesting impaired sodium handling in affected black youth.

Salt Restriction in the Treatment of Isolated Systolic and Combined Hypertension

The most recent recommendations of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) have emphasized dietary sodium (salt) restriction as a major lifestyle intervention with which to reduce blood pressure in those with “prehypertension” and as adjunctive therapy in combination with antihypertensive drugs in those with established hypertension.1 The benefit of a reduction in salt intake in lowering blood pressure in many, but not all hypertensive subjects, is well known and widely accepted on the basis of numerous trials.2 Nonetheless, debate continues regarding the extent of restriction required and whether all forms of hypertension benefit. He et al, in this issue of Hypertension , provide new insight into the impact of modest salt restriction on blood pressure in those with isolated systolic hypertension, as well as those with combined systolic–diastolic hypertension by reanalyzing data from 4 previous trials that they conducted.3 Among 24 subjects with isolated systolic hypertension and an average age of 63 years, a mean reduction of urinary sodium excretion from 175 to 87 mmol/d for 1 month resulted in an average decrease of 10/1 mm Hg (systolic/diastolic) (baseline 166/86; intervention 156/85) in blood pressure. These findings are similar to much larger drug intervention studies in such subjects demonstrating significant decreases in systolic pressure without appreciable changes in diastolic pressure. Among 88 younger (average age, 55 years) subjects with systolic/diastolic hypertension, a reduction from 175 to 98 mmol/d in average sodium excretion resulted in an …

Salt loading induces redistribution of the plasmalemmal Na/K-ATPase in proximal tubule cells

We have reported that digitalis-like substances (cardiotonic steroids), including marinobufagenin (MBG), induce endocytosis of the plasmalemmal Na/K-ATPase in LLC-PK1 cells. The current report addresses the potential relevance of plasmalemmal Na/K-ATPase redistribution to in vivo salt handling. Male Sprague-Dawley rats were given 1 week of a high salt (4.0% NaCl) or normal salt (0.4% NaCl) diet. Urinary sodium excretion, as well as MBG excretion, was monitored, and proximal tubules were isolated using a Percoll gradient method. Tubular (86)Rb uptake, Na/K-ATPase enzymatic activity, and Na/K-ATPase alpha1 subunit density were determined. The high salt diet increased urinary sodium (17.8 +/- 1.8 vs. 2.5 +/- 0.3 mEq/day, P < 0.01) and MBG excretion (104 +/- 12 vs. 26 +/- 4 pmol/day), and decreased proximal tubular (86)Rb uptake (0.44 +/- 0.07 vs. 1.00 +/- 0.10, P < 0.01) and Na/K-ATPase enzymatic activity (5.1 +/- 1.1 vs. 9.9 +/- 1.6 micromol/mg pr/hr, P < 0.01) relative to the normal diet. Proximal tubular Na/K-ATPase alpha1 protein density was decreased in the plasmalemma fraction but increased in both early and late endosomes following the high salt diet. In rats fed a high salt diet, anti-MBG antibody caused a 60% reduction in urinary sodium excretion, substantial increases in proximal tubule (86)Rb uptake, and Na/K-ATPase enzymatic activity, as well as significant decreases in the early and late endosomal Na/K-ATPase alpha1 protein content. These data suggest that redistribution of the proximal tubule Na/K-ATPase in response to endogenous cardiotonic steroids plays an important role in renal adaptation to salt loading.

Chronic administration of adrenomedullin attenuates the hypertension and increases renal nitric oxide synthase in Dahl salt-sensitive rats

Adrenomedullin reduces systemic blood pressure and increases urinary sodium excretion partly through the release of nitric oxide. We hypothesized that chronic adrenomedullin infusion ameliorates salt-sensitive hypertension and increases the expression of renal nitric oxide synthase (NOS) in Dahl salt-sensitive (DS) rats, because the reduced renal NOS expression promotes salt sensitivity. DS rats and Dahl salt-resistant (DR) rats were fed a high sodium diet (8.0% NaCl) for 3 weeks. The high sodium diet resulted in an increase in blood pressure and a reduction of urinary sodium excretion in association with increased renal adrenomedullin concentrations and decreased expression of renal neuronal NOS (nNOS) and renal medullary endothelial NOS (eNOS) in DS rats compared with DR rats. Chronic adrenomedullin infusion partly inhibited the increase of blood pressure and proteinuria in association with a restoration of renal nNOS and medullary eNOS expression in DS rats under the high sodium diet. The immunohistochemical analysis revealed that the restored renal nNOS expression induced by chronic adrenomedullin infusion may reflect the restoration of nNOS expression in the macula densa and inner medullary collecting duct. These results suggest that adrenomedullin infusion has beneficial effects on this hypertension probably in part through restored renal NOS expression in DS rats.

Neurohormonal activation, the renal dopaminergic system and sodium handling in patients with severe heart failure under vasodilator therapy

The benefits of tailoring therapy with vasodilators in patients with severe heart failure are well documented, but this may lead to neurohormonal activation and sodium retention. Renal dopamine has local natriuretic actions and interacts with other hormones involved in renal sodium handling. The aim of the present work was to determine the effects of arterial underfilling induced by vasodilator therapy on renal sodium handling, neurohormonal activation and the activity of the renal dopaminergic system in patients with severe heart failure. For this purpose we monitored haemodynamic parameters, plasma levels of type B natriuretic peptide (BNP), catecholamines, aldosterone, renin activity (PRA), sodium and creatinine, and urinary excretion of sodium, creatinine, L-DOPA, dopamine and its metabolites, before initiation of sodium nitroprusside therapy and every 6 h thereafter (for 42 h), and again after 5 days of angiotensin-converting enzyme (ACE) inhibition, in 10 male patients with severe heart failure. The results of nitroprusside therapy were a marked increase in cardiac index and a substantial decrease in systemic vascular resistance index. Plasma levels of BNP decreased significantly, while PRA, noradrenaline and aldosterone showed marked increases, resulting in a substantial reduction in urinary sodium excretion. Creatinine clearance was not affected. Urinary dopamine and dopamine metabolites increased in response to nitroprusside therapy. After 5 days of ACE inhibition, urinary sodium returned to baseline values, while urinary dopamine was markedly reduced. These results suggest that the renal dopaminergic system is activated in patients with severe heart failure by stimuli leading to sodium renal reabsorption.

Sustained hypersensitivity to angiotensin II and its mechanism in mice lacking the subtype-2 (AT2) angiotensin receptor.

The vast majority of the known biological effects of the renin-angiotensin system are mediated by the type-1 (AT1) receptor, and the functions of the type-2 (AT2) receptor are largely unknown. We investigated the role of the AT2 receptor in the vascular and renal responses to physiological increases in angiotensin II (ANG II) in mice with targeted deletion of the AT2 receptor gene. Mice lacking the AT2 receptor (AT2-null mice) had slightly elevated systolic blood pressure (SBP) compared with that of wild-type (WT) control mice (P < 0.0001). In AT2-null mice, infusion of ANG II (4 pmol/kg/min) for 7 days produced a marked and sustained increase in SBP [from 116 +/- 0.5 to 208 +/- 1 mmHg (P < 0.0001) (1 mmHg = 133 Pa)] and reduction in urinary sodium excretion (UNaV) [from 0.6 +/- 0.01 to 0.05 +/- 0.002 mM/day (P < 0.0001)] whereas neither SBP nor UNaV changed in WT mice. AT2-null mice had low basal levels of renal interstitial fluid bradykinin (BK), and cyclic guanosine 3', 5'-monophosphate, an index of nitric oxide production, compared with WT mice. In WT mice, dietary sodium restriction or ANG II infusion increased renal interstitial fluid BK, and cyclic guanosine 3', 5'-monophosphate by approximately 4-fold (P < 0.0001) whereas no changes were observed in AT2-null mice. These results demonstrate that the AT2 receptor is necessary for normal physiological responses of BK and nitric oxide to ANG II. Absence of the AT2 receptor leads to vascular and renal hypersensitivity to ANG II, including sustained antinatriuresis and hypertension. These results strongly suggest that the AT2 receptor plays a counterregulatory protective role mediated via BK and nitric oxide against the antinatriuretic and pressor actions of ANG II.

A calcium-channel blocker, amlodipine, attenuates insulin antinatriuresis but does not modulate insulin-mediated attenuation of cardiovascular reactivity in healthy man.

Insulin exerts an antinatriuretic effect when administered acutely in vivo. Interestingly, insulin fails to reduce sodium excretion in rats receiving verapamil. The present study was undertaken in order to investigate whether the calcium-channel blocker amlodipine attenuates the antinatriuretic effect of insulin in humans. Eight healthy lean men (32 +/- 2 years) were investigated on three different occasions; i.e. time-control, insulin infusion alone, and insulin infusion following pretreatment with amlodipine (5 mg x 1 during 10 days). During the experiments renal haemodynamics (insulin and PAH clearances) and segmental tubular sodium handling (sodium and lithium clearances) were investigated. The cardiovascular reactivity was also assessed by a graded noradrenaline infusion at the end of each experiment. Insulin infusion alone was accompanied by a significant 50% reduction in urinary sodium excretion. Following amlodipine pretreatment, euglycaemic insulin infusion was associated with an attenuated antinatriuretic response and the cumulative sodium excretion following 135 min of insulin infusion was significantly higher (24 +/- 4 vs 18 +/- 3 mmol; P < 0.05) as compared to insulin infusion alone. No significant differences in the proximal and distal tubular sodium handling respectively, were seen following CCB pretreatment. The results also show that the doses of noradrenaline required to increase the basal mean arterial blood pressure by 10 mmHg (262 +/- 38 vs 150 +/- 25 ng/kg/min; P < 0.05) and by 20 mmHg (431 +/- 36 vs 250 +/- 38 ng/kg/ min; P < 0.05) respectively, were significantly higher during the insulin infusion than during the time-control experiment. Pretreatment with amlodipine did not further modulate the cardiovascular reactivity. Pretreatment with a calcium-channel blocker, amlodipine, attenuates the antinatriuretic effects of insulin leading to a significantly higher cumulative sodium excretion at the end of insulin infusion, which may be of clinical importance. Moreover, insulin attenuates the cardiovascular reactivity to a graded noradrenaline infusion, suggesting that insulin causes vasodilatation in healthy man.

Antihypertensive Effect of Chronic KT3-671, a Structurally New Nonpeptide Angiotensin AT1-Receptor Antagonist, in Stroke-Prone Spontaneously Hypertensive Rats

KT3-671 (2-propyl-8-oxo-1-[(2-(1H-tetrazole-5-yl)biphenyl-4-yl)methyl]-4,5,6,7-tetrahydro-cycloheptimidazole), a structurally new nonpeptide angiotensin AT1-receptor antagonist, was administered orally and repeatedly to 15-week-old stroke-prone spontaneously hypertensive rats for 7 weeks; and its effects on blood pressure, heart rate, renal function, plasma renin concentration (PRC), plasma aldosterone concentration (PAC) and hypertension-related tissue damage in the brain, heart, kidney and mesenteric artery were investigated. KT3-671 at a dose of 3 or 10 mg/kg, p.o. per day prevented development of hypertension and produced a significant and consistent reduction of blood pressure in a dose-dependent manner. Enalapril at a dose of 10 mg/kg per day produced cardiovascular effects similar to those of KT3-671 at 10 mg/kg. Despite marked reduction in blood pressure, neither KT3-671 nor enalapril affected the heart rate. KT3-671 at 10 mg/kg produced a transient and significant reduction of urinary sodium excretion in the second week, but did not affect renal function at any other time during the experimental period. Both KT3-671 at 10 mg/kg and enalapril at 10 mg/kg produced a significant increase in PRC and showed a tendency to decrease PAC. Repeated administration of KT3-671 reduced the severity of the pathological changes in the kidney. These results suggest that KT3-671 is a potentially useful antihypertensive drug.

Effects of Atrial Natriuretic Peptide on Angiotensin II-Induced Antinatriuresis in Anesthetized Dogs.

Inhibitory effects of atrial natriuretic peptide (ANP) on angiotensin II (ANG II)-induced renal responses were examined in anesthetized dogs. ANG II (5 ng/kg per min) was infused intravenously and changes in renal hemodynamics and urine formation were compared between the ANP (10 ng/kg per min)-infused kidney and the contralateral vehicle-infused (control) kidney. ANG II reduced absolute and fractional urinary sodium excretion in both the ANP-infused kidney and the control kidney. ANG II also reduced glomerular filtration rate in the control kidney but not in the ANP-infused kidney. The ANG II-induced reduction in urinary sodium excretion in the ANP-infused kidney was smaller than the response in the control kidney, whereas ANP did not affect the reduction in fractional sodium excretion. These results suggest that ANP prevents hypofiltration and thereby attenuates the antinatriuresis induced by ANG II.

Renal sodium handling and neurohumoral systems in patients with cirrhosis in sitting posture: effects of spironolactone and water immersion

Renal sodium handling, neurohumoral systems, and systemic hemodynamics were investigated under baseline conditions in sitting posture in 10 healthy subjects, 11 patients with cirrhosis without, and 10 patients with cirrhosis with ascites. Furthermore, the effects of head-out water immersion, 1-week spironolactone administration, or their combination was assessed in the two groups of patients. Patients without ascites exhibited a significant increase in plasma norepinephrine concentration and a tendency toward an increase in plasma aldosterone concentration. Patients with ascites had a significantly lower mean arterial blood pressure despite significant reduction of urinary sodium excretion and fractional sodium excretion as well as an increase of plasma renin activity, plasma aldosterone, and norepinephrine concentration. In patients with ascites, the increase in renal sodium excretion and fractional sodium excretion following water immersion or spironolactone was clearly augmented by the combination of the two maneuvers. The same pattern was observed in patients without ascites. Our findings (a) underscore the importance of studying hemodynamics, renal function, and neurohumoral systems also in upright posture, (b) suggest a role of sympatico-adrenergic activation and proximal sodium retention in preascitic patients, and (c) are compatible with the vasodilation hypothesis of ascites formation.

An overview of randomized trials of sodium reduction and blood pressure.

To test for effects on systolic and diastolic blood pressure and to provide precise estimates of their magnitude, we conducted an overview of randomized clinical trials that aimed to reduce the intake of sodium in human subjects. We excluded from pooled analyses trials with confounded designs, those that compared intake levels beyond the usual range in the population, and those without published reports. Two reviewers abstracted information in duplicate and differences were reconciled. Twenty-three trials with outcome data from an aggregate of 1,536 subjects were included. Data were pooled both separately for hypertensive and normotensive subjects and for all trials combined. With the use of sample size weighting, blood pressure reductions (net of controls) were 4.9 +/- 1.3/2.6 +/- 0.8 mm Hg (systolic and diastolic, respectively, with 95% confidence limits) in hypertensive subjects and 1.7 +/- 1.0/1.0 +/- 0.7 mm Hg in normotensive subjects. The combined blood pressure reductions were 2.9 +/- 0.8/1.6 +/- 0.5 mm Hg. These changes were associated with mean reduction of urinary sodium excretion ranging from 16 to 171 mmol/24 hr for individual trials. A dose-response relation across trials was found, both in normotensive and in hypertensive subjects. These results indicate that sodium reduction lowers mean blood pressure in both hypertensive and normotensive individuals for periods of at least several months. The findings are highly consistent with results of observational epidemiological studies and have implications for preventive strategies of blood pressure control.

Long term reduction in sodium balance: possible additional mechanism whereby nifedipine lowers blood pressure.

To assess the changes in sodium excretion and sodium balance after withdrawal of long term nifedipine. Single blind, placebo controlled study in patients receiving fixed sodium and potassium intakes. Blood pressure unit of a teaching hospital in south London. Eight patients with mild to moderate uncomplicated essential hypertension who had been taking nifedipine 20 mg twice daily for at least six weeks. Withdrawal of nifedipine and replacement with matching placebo for one week. Urinary sodium excretion and cumulative sodium balance, body weight, plasma atrial natriuretic peptide concentrations, plasma renin activity and aldosterone concentrations, and blood pressure. During nifedipine withdrawal there was a significant reduction in urinary sodium excretion (day 1: -62.7 mmol/24 h; 95% confidence interval -90.3 to -35.0) and each patient retained a mean of 146 (SEM 26) mmol sodium over the week of replacement with placebo. Body weight and plasma atrial natriuretic peptide concentrations increased during the placebo period and seemed to be associated with the amount of sodium retained. Systolic blood pressure rose from 157 (9) to 165 (9) mmHg (95% confidence interval of difference -7.1 to 22.1) when nifedipine was replaced with matching placebo, and the rise seemed to be related to the amount of sodium that was retained. Nifedipine causes a long term reduction in sodium balance in patients with essential hypertension. This long term effect may contribute to the mechanism whereby nifedipine lowers blood pressure.

Hormonal responses to large paracentesis: Are discordant results due to technologic differences?

The use of paracentesis has recently been reproposed as a safe and effective alternative to diuretics for management of ascites. We have investigated the clinical and biochemical effects of large-volume paracentesis in 19 cirrhotics with tense ascites, and the relative changes in the hormones involved in sodium and water renal handling. Plasma renin activity (PRA), aldosterone (PA), and arginine vasopressin (AVP) levels and conventional liver and renal function tests were measured before and 1, 2 and 7 days after the paracentesis. No complications were observed, but patients regained 37% of the weight lost after 1 wk. Percent weight regained was significantly and directly correlated with PA concentration measured before the paracentesis. No changes were recorded after paracentesis in biochemical and clinical data, except for a significant drop in diastolic blood pressure. No changes in AVP levels were observed. A signficant increse in PA occured after paracentesis, with a maximum peak after 48 h. The increase in PA was not accompanied by changes in PRA, but was associated with a reduction of urinary sodium excretion. A relevant fraction of body aldosterone was confined to the ascitic fluid. We conclude that the clinical results of a large-volume paracentesis can be predicted in part on the basis of PA measurement, and that removal of ascites is followed by an increase of PA of uncertain origin and effectiveness.