SUMMARY This study was undertaken to formulate reliable confidence limits for the relationship between nocturnal and 24-hour urine sodium (Na) excretion for use in population compliance studies. Urine excretions were measured in 12 white and 12 black men at three levels of sodium (Na) intake (10, 200, and 400 mEq/day) for 7 days. Nocturnal Na, chloride (Cl), and Cl determined by titrator stick were all highly correlated (r2= 0.86, p < 0.001) with 24-hour U N .V. No significant difference could be attributed to race. Discriminate analysis revealed that the subjects could be categorized with respect to Na intake with accuracies of 95%, 90%, and 85% (low, middle, and high Na intake respectively) by means of two nocturnal urine Cl titrator stick measurements. In addition, two such measurements showing nocturnal U a V < 10 mEq indicated with 95% accuracy that 24-hour U Nl V was < 60 mEq. According to these data, measurement of nocturnal Na or Cl excretion is a useful means of assessing compliance to a low sodium intake, and the titrator sticks are a convenient and inexpensive tool. (Hypertension 4:494-498, 1982) KEY WORDS • sodium • chloride • hypertension • diurnal rhythms • nutrition T HE hypothesis that habitual high-sodium intake is a contributing factor in the development of arterial hypertension was first proposed in the Nei Ching,' a Chinese text that is the oldest known collection of medical writings. Since that time the hypothesis has been inferred from numerous epidemiological, clinical, and experimental animal studies.2 " 13However, in testing the hypothesis, it has been difficult to estimate individual sodium consumption; collection of multiple 24-hour urine specimens, use of dietary recall, and analysis of duplicate diets have been unsatisfactory research tools.To find a precise method for estimating sodium intake, we first investigated whether the relationship between nocturnal and 24-hour sodium excretion might be different in whites and blacks. In addition, we evaluated simple means to assess compliance that could be used in the home as well as in the laboratory, and provide reliable confidence limits. MethodsWe recruited 12 white and 12 black men ranging in age from 19 to 32 years. They were either students at

SUMMARY Primary aldosteronism is an uncommon cause of hypertension but one of particular interest because of its distinctive pathophysiological mechanism of blood pressure elevation. Aldosterone has been associated with increased Na + ,K+-adenosine triphosphatase (ATPase) activity, but there is controversy over which sodium transport parameters are responsible for this increase. We measured intracellular sodium, ouabain-sensitive and ouabain-insensitive sodium efflux, and the number of Na + ,K + -ATPase sites of washed erythrocytes, as well as Na+-Li + countertransport and the L1+-K+ cotransport rate constant of lithium-loaded red blood cells (RBCs) in six patients with primary aldosteronism and in 50 normal subjects. Ouabain-sensitive sodium efflux was significantly (p< 0.001) higher for the primary aldosteronism patients than for normal subjects (1.85 ± 0.29 vs 1.51 ± 0.21 mmol/L RBC/hr) even though the intracellular sodium concentration (7.2 ± 1.5 vs 6.7 ± 1.9 mM) and the number of the Na+,K+-ATPase sites per RBC (331 ± 52 vs 385 ± 97) were not increased. The elevated sodium efflux appeared to be due to a significant (p<0.001) increase in the rate constant (1.60 ± 0.12 x 10-" vs 1.28 ± 0.15 x 10-" mmol/site/hr) of the ouabain-sensitive sodium efflux. The rate constant decreased significantly (p<0.01) after treatment.

To test the hypothesis that the antihypertensive effect of the calcium channel blocking drug nitrendipine is in part related to natriuresis, we gave 16 subjects (8 normal, 8 hypertensive) placebo for 8 days followed by nitrendipine titrated to 20 mg twice daily for 8 days. The same diet was prepared for each meal for the entire study. Sodium intake was fixed for each subject and averaged 150 mEq/day. All urine was collected every day. Blood was drawn at the end of the placebo and nitrendipine periods for renin, aldosterone, and norepinephrine values. Nitrendipine caused a significant increase (p less than 0.05) in cumulative sodium excretion of 161 mEq over 7 days in the normal subjects and 103 mEq in hypertensive subjects. Potassium excretion was unaffected. In both hypertensive and normal subjects, plasma renin and plasma norepinephrine activity increased significantly (p less than 0.05), while plasma aldosterone levels did not change. Upright systolic blood pressure decreased significantly (p less than 0.05) in both groups, whereas upright diastolic blood pressure decreased only in hypertensive subjects. We conclude that blood pressure lowering effects of this drug may be in part related to natriuresis and that calcium channel blockade may dissociate plasma renin activity from that of aldosterone.

To investigate the role of potassium on blood pressure we measured serum potassium, urinary excretion of potassium and sodium, fractional excretion of potassium, urinary sodium:potassium ratio, plasma renin activity, aldosterone, and norepinephrine during dynamic maneuvers in normotensive and hypertensive subjects. After baseline measurements, we expanded intravascular volume with infusion of intravenous saline and then induced sodium and volume depletion by diuretic administration during a low sodium salt diet. These studies were performed in 431 normotensive and 478 hypertensive subjects enabling evaluation of the effects of age, race, and sex, as well as blood pressure, on the results. Among normotensives, we found that white subjects had significantly P less than 0.05) higher levels of serum and urine potassium, fractional potassium excretion and lower urinary sodium:potassium ratios than black subjects and that males had the same patterns of differences compared to females. Similar, but less consistent racial differences were seen among the hypertensive subjects. We also observed significant (P less than .05) correlations between urinary potassium excretion and body weight in both normal and hypertensive groups. In normal subjects, a significant correlation was observed between the urinary sodium:potassium ratio and blood pressure that was not seen in the hypertensives. The latter, however, displayed a significant (P less than .05) inverse relationship between serum potassium and blood pressure. Multiple regression analysis revealed that urinary potassium excretion was influenced by age, race, sex, body weight, blood pressure, creatinine clearance, renin, and aldosterone. These observations reveal important relationships between potassium homeostasis and blood pressure control that deserve further study.

Three parameters of the sodium pump, the sodium efflux rate, the intracellular sodium content (Nai) and the number of sodium, potassium ATPase sites per red blood cell (sites/rbc) were measured simultaneously on erythrocytes from normal men and women and from women taking oral contraceptives. Significant (p less than 0.002) differences were obtained between normal men and women for sodium efflux (1.68 +/- 0.15 vs 1.52 +/- 0.12 mmoles/L rbc/hr). Among the three measured parameters, there was an inverse relationship (r = -0.74) between Nai and sites/rbc and a linear correlation (r = 0.89) between efflux per site and Nai. A positive correlation (r = 0.78) between the sites/rbc and a first-order rate constant for Na efflux/rbc suggests that one component of the rate constant is the number of sites/rbc. Values for a second-order rate constant, calculated from the assumption that efflux/rbc depends on both Nai and the number of sites/rbc, were similar for normal men and women but significantly (p less than 0.001) higher for women taking oral contraceptives.