24-h Sodium Excretion Research Articles

Magnetic Resonance Measurements of Renal Blood Flow and Disease Progression in Autosomal Dominant Polycystic Kidney Disease

Whether changes in renal blood flow (RBF) are associated with and possibly contribute to cystic disease progression in autosomal dominant polycystic kidney disease (ADPKD) has not been ascertained. The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) was created to develop imaging techniques and analyses to evaluate progression. A total of 131 participants with early ADPKD had measurements of RBF and total kidney (TKV) and cyst (TCV) volumes by magnetic resonance and of GFR by iothalamate clearance at baseline and 1, 2, and 3 yr. The effects of age, gender, body mass index, hypertension status, mean arterial pressure (MAP), TKV, TCV, RBF, renal vascular resistance (RVR), GFR, serum uric acid, HDL and LDL cholesterol, 24-h urine volume, sodium (UNaE) and albumin (UAE) excretions, and estimated protein intake were examined at baseline on TKV, TCV, and GFR slopes. TKV and TCV increased, RBF decreased, and GFR remained stable. TKV, TCV, RVR, serum uric acid, UAE, UNaE, age, body mass index, MAP, and estimated protein intake were positively and RBF and GFR negatively correlated with TKV and TCV slopes. TKV, RBF, UNaE, and UAE were independent predictors of TKV and TCV slopes (structural disease progression). TKV, TCV, RVR, and MAP were negatively and RBF positively correlated with GFR slopes. Regression to the mean confounded the analysis of GFR slopes. TKV and RBF were independent predictors of GFR decline (functional disease progression). In ADPKD, RBF reduction (1) parallels TKV increase, (2) precedes GFR decline, and (3) predicts structural and functional disease progression.

Longitudinal examination of 24-h urinary iodine excretion in schoolchildren as a sensitive, hydration status–independent research tool for studying iodine status

Because worldwide iodine status (IS) depends on continuous fortification, the adequacy of IS needs to be regularly monitored. Our study aimed to evaluate IS in a longitudinal sample of healthy schoolchildren who regularly used table salt iodized with 20 microg I/g. Urine osmolality (Uosm) and 24-h urinary excretion rates of iodine (24-h UI), sodium, creatinine, and total urine volume (24-h Uvol) were measured in 1046 specimens that were collected at repeated intervals from 1996 to 2003 in a sample of 358 German children aged 6-12 y. Energy intake and food consumption were calculated from 3-d weighed dietary records that were collected in parallel to the urine samples. During the 4-y period from 1996 to 1999, the median 24-h UI increased from 87 to 93 microg I/d (P = 0.017), whereas urinary iodine concentration (UIC), Uosm, and 24-h Uvol did not change significantly. Thereafter (from 2000 to 2003), UIC stagnated and Uosm decreased (P = 0.004), whereas 24-h Uvol (P = 0.008) and 24-h UI (P = 0.002) increased. The final median 24-h UI reached 120 microg I/d. Milk, fish, egg, and meat intakes and 24-h sodium excretion were all significant predictors of IS, with an almost doubled contribution from milk intake during the second 4-y period. Our study shows a continuous improvement of IS in a longitudinal sample of German schoolchildren. This improvement was masked when UIC was used as an IS index, especially from 2000 to 2003 because of changes in hydration status. Thus, in research-oriented studies that focus on UIC measurements, hydration status can be a relevant confounder. Longitudinal analyses of 24-h UI in cohort studies may represent an alternative hydration status-independent tool to examine trends in IS and the contribution of relevant foods to IS.

Increased Sodium Intake Correlates With Greater Use of Antihypertensive Agents by Subjects With Chronic Kidney Disease

Hypertension is a common disease in patients with chronic kidney disease (CKD) and predisposes to heart disease, stroke, and progression of renal failure. In the general population, sodium restriction has been shown to improve blood pressure (BP) control, but this is not widely recommended in CKD patients. The aim of this study was to assess the sodium balance in a CKD clinic and its effect on BP management. We retrospectively reviewed charts from June 1998 through to June 2003 and included all patients with an estimated glomerular filtration rate (GFR) of <30 mL/min who completed a 24-h urine collection for sodium. Patients were divided into tertiles based upon their 24-h sodium excretion and analyzed by ANOVA. We included 141 CKD patients who had a mean (+/- SE) sodium excretion of 145.7 +/- 4.7 mmol/day. There were a significantly greater number of antihypertensive agents used with increasing sodium excretion (2.00 +/- 0.16, 2.61 +/- 0.20, and 2.77 +/- 0.19 medications, respectively for each tertile; P = .01). This difference was even more prominent when only those patients with a GFR <or=15 mL/min (n = 77) were examined (1.69 +/- 0.19, 2.52 +/- 0.27, and 3.08 +/- 0.26 medications, respectively; P = .001). Control of BP was equivalent in all groups. Multivariable analysis revealed sodium excretion (P = .00005) and age (P = .007) to be significantly associated with use of antihypertensive medication. We have demonstrated that increased sodium intake is associated with an increased number of antihypertensive medications to achieve comparable BP control in a population with CKD.

Iodine status in schoolchildren between 1996 and 2003: longitudinal 24-h urinary iodine excretion in 6–12 years old participants of the DONALD study

In Germany iodine supply was insufficient in the early nineties, but has improved in the mean time. However, a detailed longitudinal examination of the long-term trend of iodine status, especially the 24-h iodine excretion is lacking so far. Starting in 1996, we repeatedly analysed urinary iodine and sodium excretion in 24-h urine samples (n=1046) of 358 healthy 6–12 years old participants of the DONALD study who regularly used iodized household salt. Energy intake and milk consumption were calculated from dietary records collected in parallel with the urine samples. Median urinary iodine excretion (adjusted for average energy intake of 10–12 years old children (9 MJ/d) increased modestly from 87µg/d to 93µg/d (p=0.003) between 1996 and 1999 and thus lays still below the WHO recommendation of 120µg iodine intake/d for schoolchildren. During the subsequent years, iodine excretion continued to rise (p=0.001) and reached 121µg/d in 2003. Although no comparable trends were observed for milk intake and 24-h sodium excretion, both dietary measures proved to be significant determinants of individual iodine status. The present longitudinal results do not support the recently published findings (also adopted in the WHO Global Database on Iodine Deficiency Disorders) reporting that iodine status in German schoolchildren aged 6–12 years has increased abruptly between the years 1996 and 1999. Despite continuous use of iodized household salt and appropriate consumption of milk products, the median iodine excretion of the DONALD cohort did not meet the WHO reference intake until 2003. It is not yet clear, to what extent increasing iodine densities in certain foods or supplements are responsible for the prolonged positive trend. Irrespective from that, repeated measurements of 24-h iodine excretion in well characterised long-term cohorts, like the DONALD study, may represent a sensitive instrument to monitor relevant trends in iodine status.

Blood pressure control in italian nephroly clinics. results of thin-study (treatment of hypertension in italian nephrology clinics)

P-399 Key Words: Hypertension, Antihypertensive Therapy, Multicenter Trial

β-Adducin polymorphisms, blood pressure, and sodium excretion in three European populations

The associations of the β-adducin C1797T polymorphism with blood pressure (BP) and various indexes of sodium homeostasis were investigated in 388 men and 456 women, aged 18 to 60 years, recruited from three European populations (Cracow, Poland, n = 300; Novosibirsk, Russian Federation, n = 274; Mirano, Italy; n = 270). Phenotypes included 24-h ambulatory BP and urinary excretion of electrolytes and aldosterone. Subjects were genotyped for the β-adducin polymorphism. Both a population-based association study and a family-based analysis were performed. Urinary sodium excretion was higher in Cracow than in Mirano (241 v 185 mmol/24 h, P < .05) and intermediate in Novosibirsk (206 mmol/24 h). The β-adducin T allele (15.2% v 9.1%, P < .0001) was more prevalent in Mirano than in the two Slavic centers. In both population-based and family-based association analyses, there was significant heterogeneity between Slavic and Italian subjects in the phenotype–genotype relationships with β-adducin. In the Slavic centers, 24-h systolic BP was higher in T allele carriers than in CC homozygotes (122.3 v 119.7 mm Hg, P = .03), whereas this was not the case in Mirano (121.8 v 122.9 mm Hg, P = .42). In Slavic (212.6 v 233.1 mmol/24 h) as well as in Italian (166.1 v 191.5 mmol/24 h) participants, 24-h sodium excretion was lower (P = .01) in T allele carriers than in CC homozygotes. These results were confirmed in the family-based analysis of offspring using a quantitative transmission disequilibrium test. In conclusion, the frequency of the β-adducin T allele and salt intake differ across European populations. Thus, both variation in genetic background and salt intake may explain the observed heterogeneity in the phenotype–genotype relationships. Genetic determinants of complex quantitative traits such as BP can only be investigated within their epidemiologic context.

One-week losartan administration increases sodium excretion in cirrhotic patients with and without ascites.

Losartan, a highly selective angiotensin II type 1 receptor antagonist, has been reported to have a significant portal hypotensive effect in cirrhotic patients. A recent study also showed that losartan exerted a dramatic natriuretic effect in preascitic cirrhosis. The influence of losartan on renal hemodynamics and sodium homeostasis in cirrhotic patients with ascites is unclear. This study was undertaken to evaluate the renal effects of 1-week losartan treatment in cirrhotic patients with and without ascites. All 12 patients in the study received a daily oral dose of 25 mg losartan for 7 consecutive days. Effective renal plasma flow, urine volume, creatinine clearance, 24h urine sodium excretion and fractional excretion of sodium, blood urea nitrogen, and serum creatinine were measured before and after treatment. In cirrhotic patients without ascites, creatinine clearance, 24-h urinary sodium excretion, and fractional excretion of sodium were significantly increased after losartan administration. Effective renal plasma flow and serum creatinine showed almost no change after treatment. In cirrhotic patients with ascites, creatinine clearance, 24-h urinary sodium excretion, fractional excretion of sodium, and effective renal plasma flow were significantly increased after losartan administration. In addition, the magnitudes of the increases in the fractional excretion of sodium and in the 24-h urinary sodium excretion were greater in cirrhotic patients with ascites than in those without ascites. One-week treatment with losartan increases sodium excretion in association with an improvement of renal function in cirrhotic patients with and without ascites. The natriuretic effect was more profound in cirrhotic patients with ascites than in those without ascites.

Different associations of blood pressure with 24-hour urinary sodium excretion among pre- and post-menopausal women. WHO Cardiovascular Diseases and Alimentary Comparison (WHO-CARDIAC) Study.

Having found no definite relationship between blood pressure (BP) and 24h sodium excretion in women aged 48-56 years (in contrast to the results in men of the same age) in the WHO Cardiovascular Diseases and Alimentary Comparison (WHO-CARDIAC) Study, we analyzed the data to investigate whether the sodium-BP association differed between pre- and post-menopausal women. The WHO-CARDIAC is a multicenter cross-sectional study, involving, as of July 2000, 60 collaborating centers in 25 countries. In each center, 100 men and 100 women aged 48-56 years were selected randomly from the general population of the area. In this report, 2,212 women in 21 centers located in 17 countries worldwide, who had data on menopausal status, were studied. After adjustment for age, body mass index (BMI) and 24h urinary potassium excretion, 24h sodium excretion was positively and significantly associated with systolic blood pressure (SBP) [pooled regression coefficient: 0.037 (SE 0.01), P < 0.01] and with diastolic blood pressure (DBP) [0.023 (0.006), P< 0.01] in post-menopausal women. Pooled regression coefficients of sodium-BP association were not significant in pre-menopausal women (P< 0.05). Cross-center correlation analyses of the 21 centers showed that 24h sodium excretion was positively associated with SBP and DBP in both pre- and post-menopausal women, and this positive association between sodium excretion and SBP was significant in post-menopausal women (R2 = 0.23, P = 0.029). Different associations between sodium and BP were observed in women with pre- and post-menopausal status. There may be a tendency for salt sensitivity to increase at the menopause.

Effects of icatibant on the ramipril-induced decreased in renal lithium clearance in the rat.

The interaction between an inhibitor of angiotensin I converting enzyme (ramipril) and renal lithium handling was analysed in conscious, normotensive Wistar rats in the absence or the presence of a specific bradykinin B2 receptor antagonist, icatibant. The rats were treated for 5 days with ramipril (1 mg/kg/day p.o.) or its vehicle, alone or together with icatibant (0.1 mg/kg/day, s.c. infusion). Lithium chloride (8.3 mg/kg i.p.) was given as a single dose on day 5. Systolic blood pressure and heart rate were measured by tail plethysmography on day 3 (3, 9 and 15 h after ramipril administration) and renal function on day 4 (0-6 and 6-24 h urine sampling) and day 5 (0-6 h urine sampling). In another group of rats, 24 h sodium excretion was assessed during the first 4 days of ramipril treatment. Ramipril decreased renal lithium clearance (90+/-8 vs. 142+/-10 microl/min/100 g, P<0.001, n=24) and increased the fractional lithium reabsorption (74.3+/-1.9 vs. 66.7+/-1.7%, P<0.05) and plasma lithium concentration (0.108+/-0.006 vs. 0.085+/-0.004 mM, P<0.01). Alteration of renal lithium handling by ramipril was associated with a decrease in systolic blood pressure (-15% 3 h after ramipril administration) and sodium excretion (0-6 h after ramipril). The 24-h sodium excretion, however, tended to increase. Icatibant had no effect per se on renal function but attenuated the ramipril-induced decrease in renal lithium clearance (118+/-16 vs. 90+/-8 microl/min/100 g, n=12 and 24 respectively, P<0.05 one-tailed test) and systolic blood pressure. These results suggest that endogenous bradykinin contributes to the ramipril-associated alteration in renal lithium handling. Bradykinin B2 receptor-mediated vasodilation seems to be involved.

Hemodynamic and renal effects of indomethacin in losartan-treated hypertensive individuals

This study was undertaken to examine whether prostaglandin (PG) inhibition with indomethacin interferes with angiotensin II receptor blockade (losartan) during treatment for arterial hypertension. In a double-blind crossover design 10 patients with essential arterial hypertension and treated with losartan were randomized to supplementary treatment with indomethacin or placebo for 1 week, with a 2-week washout period interposed. At the end of each treatment period the following examinations were performed, preceded by 4 days on sodium-fixed diet: 24-h blood pressure (BP), 24-h sodium excretion (U NaV), supine BP, glomerular filtration rate (GFR), renal resistive index (RRI), extracellular fluid volume (ECV), sodium clearance (Cl Na), body weight, peripheral blood flow (PBF), and plasma concentrations of aldosterone, renin (PRC), and atrial natriuretic peptide (ANP). Indomethacin did not change BP. Indomethacin increased weight ( P < .05) and ECV ( P < .05). A nonsignificant decrease in U NaV was seen after indomethacin, as in 24-h Cl Na. Conversely, in the laboratory in the supine position Cl Na increased after indomethacin ( P = .05). Indomethacin increased plasma ANP ( P < .01). No changes were observed in GFR, RRI, PBF, PRC, or plasma aldosterone. Thus indomethacin did not attenuate the antihypertensive effect of losartan, neither was peripheral blood flow affected. Indomethacin caused sodium retention in the nonresting situation, which was not counterbalanced by the increased Cl Na in the resting supine position. The observed changes during prostaglandin (PG) inhibition seem most likely due to lack of PG “protection” of renal function, when the sympathetic nervous system is activated throughout the day.

Serum digoxin-like immunoreactive factor in children and its relation to sodium metabolism.

Serum digoxin-like immunoreactive factor (DLIF), an endogenous substance that cross-reacts with antidigoxin antibodies, was assessed (fluorescence polarization immunoassay) in children (n = 134) aged 5-16 y, who had never been treated with cardiac glycosides. DLIF was found in 50% of serum samples at a mean concentration of 0.16 +/- 0.06 ng/ml (range 0.03-0.35 ng/ml). Although the study population as a whole was apparently homogeneous with regard to serum sodium content, and none had clinical signs of sodium imbalance, children with DLIF showed significantly lower natraemia (p = 0.0002), higher urinary concentration (p = 0.001) and fractional excretion (p = 0.001) of sodium, and increased systolic blood pressure (p = 0.009) compared with children without DLIF. Inverse correlations were found between DLIF concentration and serum sodium (p < 0.01), urine sodium content (p < 0.001), 24-h sodium excretion (p < 0.001), systolic (p < 0.001) and diastolic (p < 0.01) blood pressure. These findings suggest that sodium handling is different in children with and without DLIF, since this material seems to be released preferably in subjects who show a trend towards negative sodium balance. Such an association suggests that DLIF may be a physiologically relevant material involved in sodium homeostasis.

Low-dose Diuretic and/or Dietary Sodium Restriction when Blood Pressure Is Resistant to ACE Inhibitor

Aim: To compare the efficacy of indapamide (1.25 mg daily) and low-salt diet (< 100 mmol/day) separately and in combination in essential hypertensive patients with inadequate BP response to perindopril. Design and Methods: Randomized double-blind, double-dummy, crossover design. The randomized treatments were indapamide 1.25 mg daily, sodium chloride 80 mmol daily, the combination of indapamide and sodium chloride and placebo. All patients received perindopril 4 mg daily and maintained a low-sodium diet. Results: 19 patients entered and 17 completed the study. Prior to randomization, average clinic sitting blood pressure was 162/101 mmHg and average 24-h urine sodium excretion was 157 mmol/day. Compared to the phase in which patients received perindopril with sodium repletion, clinic and ambulatory BPs were significantly reduced (p < 0.01) in all the other phases. Indapamide had a greater effect on BP than dietary sodium restriction, and in combination their effects were additive. The effect of indapamide on ambulatory BP persisted throughout 24 h, but the effect of the low-salt diet was predominantly observed during waking hours. Conclusions: In hypertensives with BP resistant to the angiotensin converting enzyme (ACE) inhibitor perindopril, the diuretic indapamide had greater additional efficacy and longer duration of action than dietary sodium restriction. In combination they had additive effects on BP.

The INTERSALT Study: background, methods, findings, and implications

The INTERSALT Study is a standardized, worldwide epidemiologic study of large sample size (n = 10079 men and women aged 20-59 y from 32 countries) that tested both within- and cross-population prior hypotheses on 24-h sodium excretion and blood pressure. For individuals, a significant, positive, independent linear relation between 24-h sodium excretion and systolic blood pressure (SBP) was found. With multivariate adjustment for underestimation, the estimated effect of a sodium intake higher by 100 mmol/d was higher SBP/DBP (diastolic blood pressure) by approximately 3-6/0-3 mm Hg. This relation prevailed for both men and women, for younger and older people, and for 8344 people without hypertension. In tests of prior cross-population hypotheses (n = 52), significant, independent relations were found between sample 24-h median urinary sodium excretion and sample median SBP and DBP, prevalence rate of hypertension, and slope of SBP and DBP from age 20 to 59 y (median sodium intake greater by 100 mmol/d was associated with a 30-y increase in SBP/DBP, i.e., at the age of 55 y compared with 25 y, of 10-11/6 mm Hg. The INTERSALT results, which agree with findings from other diverse studies, including data from clinical observations, therapeutic interventions, randomized controlled trials, animal experiments, physiologic investigations, evolutionary biology research, anthropologic research, and epidemiologic studies, support the judgment that habitual high salt intake is one of the quantitatively important, preventable mass exposures causing the unfavorable population-wide blood pressure pattern that is a major risk factor for epidemic cardiovascular disease.

Effects of Lisinopril on Stress-Induced Peak Blood Pressure and Sodium Excretion

A stress test was performed before (S1) and after a 1-month treatment period (S2) in patients with essential hypertension, randomly allocated to receive either an angiotensin-converting enzyme inhibitor (ACEI), lisinopril (n = 10), or placebo (n = 10). The two groups were similar with regard to systolic and diastolic blood pressure (SBP, DBP), body weight, renal function, and 24-h sodium excretion. At S1, stress induced a significant increase in SBP of 18 +/- 9 mm Hg and in DBP of 10 +/- 6 mm Hg and a significant reduction in sodium excretion from 258 +/- 105 to 204 +/- 72 mumol/min. Stress-induced sympathetic stimulation was assessed by a significant increase in urinary norepinephrine (NE) excretion from 21 +/- 10 to 26 +/- 10 micrograms/g creatinine. One-month treatment by placebo did not change stress-induced BP reactivity, sodium retention, or urinary NE excretion. In the lisinopril group, rest and stress BP were significantly reduced by the treatment. Stress-induced sodium retention was higher after 1-month placebo treatment (72 +/- 78 vs 48 +/- 67 mumol/min), whereas this retention was significantly reduced by lisinopril (13 +/- 27 vs 69 +/- 60 mumol/min).

The relationship between blood pressure and sodium and potassium excretion during the day and at night.

The relationships between blood pressure and the urinary excretion rates of sodium and potassium during the day and at night were investigated. A total of 160 participants (135 normotensive subjects and 25 untreated patients with essential hypertension) were examined using ambulatory blood pressure monitoring and timed urine collections during waking and sleeping hours. Blood pressure averaged 126/79 mmHg during waking hours and 107/62 mmHg during sleep. More sodium, potassium and aldosterone were excreted during the daytime, but the natriuretic substance kallikrein was excreted at a fixed rate throughout the 24 h. During waking hours there was poor correlation between blood pressure and urinary sodium and potassium excretion. By contrast, at night when the aldosterone: kallikrein ratio fell, the sodium and potassium excretion rates were positively correlated with blood pressure. Pressure natriuresis, not apparent during waking hours, may be unmasked at night when the balance between sodium-retaining and sodium-losing mechanisms favours natriuresis. Thus, the relationship between blood pressure and 24-h sodium excretion, usually considered to show the influence of salt intake on blood pressure, may also reflect pressure-induced natriuresis, if urine is more completely collected at night than during the day, and in circumstances favouring sodium retention during the day and sodium loss during sleep.

Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of bumetanide

The pharmacokinetics and pharmacodynamics of bumetanide were evaluated after intravenous (i.v.) administration of the same total dose of bumetanide in different lengths of infusion times, 10 s (treatment I), 1 h (treatment II), and 4 h (treatment III) to rabbits. The fluid loss in urine was immediately replaced volume for volume with i.v. infusion of lactated Ringer's solution. Some pharmacokinetic parameters of bumetanide were infusion time-dependent and it might be due to the saturable metabolism of bumetanide. For example, the mean values of CL (13.6, 25.3 vs 18.2 ml min-1 kg-1), MRT (9.70, 10.6 vs 21.8 min), Vss (128, 217 vs 378 ml kg-1), and CLNR (2.71, 9.24 vs 6.44 ml min-1 kg-1) increased when the same dose of bumetanide was infused in 1 h or 4 h. However, the mean values of t1/2, and CLR were not significantly different among three treatments. The diuretic effects (urine outputs and urinary excretions of sodium and chloride) increased significantly in 1 and 4 h of infusion although the total amounts of urinary excretion of unchanged bumetanide were 21.8 and 20.5 per cent lower in treatments II and III, respectively, when compared with the value in treatment I; the mean values of 8-h urine outputs were 373, 922, and 1030 ml for 10s, 1 h, and 4 h of infusion, respectively, and the corresponding values for 24-h sodium excretions were 49.0, 82.8, and 121 mmol, and for chloride were 47.5, 71.1, and 114 mmol. It could be due to the higher diuretic efficiencies in treatments II and III. Plasma concentrations of bumetanide, and hourly urine outputs and hourly urinary excretion rates of bumetanide, sodium, potassium, and chloride during the apparent steady state (between 1 and 4 h) in the 4 h infusion study were fairly constant.

The Bergen blood pressure study: sodium intake and ambulatory blood pressure in offspring of hypertensive and normotensive families.

Sodium intake, estimated by the 24-h urine sodium excretion, was assessed in 39 offspring of hypertensive families and 37 offspring of normotensive families. The family history of hypertension or normotension was defined according to parental BP data from two surveys conducted 27 years apart. Urine-sodium excretion was similar in offspring of hypertensive and normotensive families, averaging 136 and 137 mmol/24 h, respectively. Monitored by non-invasive methodology in the urine sampling period, the average 24-h ambulatory blood pressure (BP) was approximately 10/10 mmHg higher in offspring of hypertensive than normotensive families. The clinically and statistically significant differences in BP between groups could not be explained by differences in sodium intake. After adjustment for confounding variables, the BP was not associated with the sodium excretion in the material as a whole or in either offspring group.

Weight reduction lowers blood pressure independently of salt restriction.

The existence of a link between obesity and hypertension is nowadays universally accepted; however, there are still some doubts about the fact that weight reduction induces a significant long-term decrease in blood pressure. This clinical trial aimed at evaluating the effects of marked weight loss (at least 30% of excess body weight) induced by a low-energy (600 Kcal), normal sodium diet in severely obese patients, on blood pressure at rest and during sympathetic stimulation. Eight of the 20 patients initially recruited for the study were able to reach the therapeutical goal and brought their body weight from 107 +/- 6 to 91 +/- 4 kg. Their blood pressure (BP) at rest was at the same time reduced from 137/81 +/- 5/4 to 122/74 +/- 4/4 mmHg. Also, blood pressure measured during three different stimuli (cold pressor test, handgrip and mental arithmetic test) was lowered by this nonpharmacological means. These effects are related solely to weight reduction, since no change in salt intake occurred, as demonstrated by measurements of the 24-h sodium excretion test (191 +/- 13 vs 185 +/- 10 mEq/24 h). In conclusion, these results support the hypothesis that a drastic weight loss, independently of salt restriction, significantly reduces BP at rest and during stimulation of the adrenergic nervous system.

Preliminary Report of the Cardiovascular Diseases and Alimentary Comparison Study

The relationship between blood pressure and dietary constituents including potassium, sodium, calcium, and protein was studied in 183 randomly selected men and women, 50-54 years of age. Twenty-five of the subjects were drug-controlled hypertensive patients. Subjects were investigated by automated BP measurements, 24-h urine collection, and blood sampling. Mean systolic BP (SBP) was 119 +/- 17 mm Hg, placing the sample between Shanghai and Sweden on the distribution chart of the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. Salt intake estimated by 24-h sodium excretion was 8.5 +/- 3.4 g/day, between Australia and Okinawa on the distribution chart. Potassium was 48.55 +/- 20 20 mEq/day, between Urumqi (China), and Beppu and Ohda (Japan). Calcium was 162.3 +/- 89.9 mg/day. Urea nitrogen, which might reflect protein intake, was 9.5 +/- 3.1 g/day. Cholesterol was 195.1 +/- 38.1 mg/dl, between Brazil and Hirosaki. The Israeli results, as well as the data on other countries participating in the CARDIAC Study, show wide variability in the profiles generated by the investigated parameters. Each parameter placed Israel with a different CARDIAC Study group.

Central role for sodium in the pathogenesis of blood pressure changes independent of angiotensin, aldosterone and catecholamines in type 1 (insulin-dependent) diabetes mellitus.

We studied 73 Type 1 (insulin-dependent) diabetic patients, 18 to 50 years of age, with a diabetes duration of more than five years. Group 1: normal urinary albumin excretion below 30 mg per 24 h (n = 19); group 2: microalbuminuria, 30-300 mg per 24 h (n = 36); and group 3: diabetic nephropathy, above 300 mg per 24 h (n = 18). Fifteen nondiabetic persons matched for sex and age served as control subjects. The sodium intake evaluated on the basis of 24-h urine sodium excretion was similar in patients and control subjects. Blood pressure in groups 1 and 2 and control subjects was below 160/95 mmHg. The blood pressure was increased in group 3 as compared with the other groups (systolic/diastolic 161 +/- 22/101 +/- 9 mmHg vs 131 +/- 13/84 +/- 10, mean +/- SD, p less than 0.0001). Exchangeable sodium was increased in patients (p less than 0.01) and correlated to the mean blood pressure (n = 70, r = 0.41, p less than 0.01). Extracellular volume was increased in patients (p less than 0.05), whereas plasma volume was normal. Supine serum angiotensin II was suppressed in the patients (p less than 0.001). A negative correlation was found between mean blood pressure and supine serum aldosterone (n = 68, r = -0.24, p less than 0.05), and exchangeable sodium and aldosterone (n = 66, r = -0.36, p less than 0.002) in all patients. The catecholamine levels were also suppressed or normal in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)