A diurnal rhythm in water and electrolyte excretion in man has been described by several investigators. Kleitman (1) reported decreased urine flow and chloride excretion during sleep as compared to "waking" hours, and suggested decreased blood pressure during sleep as the cause.Simpson (2, 3) confirmed these observations in young healthy adults who ingested the same amount of water at hourly intervals throughout 24 hours and suggested the acidosis of sleep, with the resultant intracellular shift of chloride and water, as a possible mechanism for the positive balance of these substances during sleep. Manchester (4) studied the 24 hour variations of water and mineral balance in two epileptic children on graded activity. He found that the maximum excretion of water, sodium, potassium and chloride occurred from 6:00 A.M. to 12:00 midnight, the minimum excretion from 12 midnight to 6:00 A.M. He concluded that the diurnal variation of water and mineral excretion is related to sleep rather than to changes in physical activity. Simpson (5) was unable to affect the cycle by means of dehydration, fasting, changes in posture or short periods of sleep during the day. Norn (6) reported a reversal of the cycle with respect to time in a night watchman who obtained his normal complement of sleep, during the day. Brod (7) showed that normal subjects have depressed endogenous "creatinine" clearances at night associated with diminished urine flow.It has been adequately demonstrated that the diurnal rhythm in water and electrolyte excretion may be absent or reversed in pathologic states. Fishberg (8) renal factor or to an increase in cardiac output in the prone position. In heart failure (9) the nocturia is explained on the basis of increased cardiac output and decreased renal venous pressure in the prone position. Brod (7), using the endogenous "creatinine" clearance as a measure of glomerular filtration and the "creatinine" U/P ratio as an indication of tubular reabsorption of water, demonstrated that the nocturia of congestive failure is associated with both a rise in glomerular filtration and decreased tubular reabsorption of water during sleep. In glomerulonephritis, however, the nocturia was due primarily to decreased water reabsorption, the filtration rate remaining fairly constant throughout 24 hours. Breed and Schreiner (10) have shown that some patients with essential hypertension have nocturia associated with a reversal of the normal diurnal pattern for chloride excretion and endogenous "creatinine" clearance.Because of the obscurity of the mechanism controlling this diurnal cycle of salt and water excretion and its importance in the treatment of congestive heart failure we have undertaken a study of the 24 hour variations of renal hemodynamics in normal subjects and in subjects with congestive heart failure. The present paper deals with normal subjects alone. METHODSSimultaneous endogenous "creatinine," inulin and paminohippurate, free and total (free plus conjugated), clearances were determined in 18 normal male subj...

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CHLOROTHIAZIDE lowers arterial blood pressure in hypertensive patients under either acute or long-term administration. The antihypertensive action of this substance is complex. In some instances, the drop in blood pressure is due to a reduction in cardiac output produced by contraction of the intravascular space resulting from its saluretic effect1 while in others it is due to a decrease in peripheral vascular resistance.2The purpose of this investigation was to make a comparative study in the same patient of the effect of the acute and long-term administration of chlorothiazide upon systemic hemodynamics. Material and MethodsNineteen observations were made in 12 patients with essential hypertension. The effect of a single intravenous dose of 500 mg. was studied in 10 instances and that of prolonged oral administration of 500 mg. every 6 hours in nine.The patients were at rest on low-salt diet and placebo. Basal and casual blood pressure readings were taken daily. As soon as these were stabilized, mean arterial blood pressure and cardiac output under basal conditions were determined. These studies were repeated from 50 to 110 minutes following the intravenous applieation of chlorothiazide (average 70 minutes). Administration of the drug was continued by mouth until pressure readings were stabilized. This took place within 8 to 31 days (average 15 days) after which the sanme studies were repeated. Mean blood pressure was taken directly at the left humeral artery with an electronic oscilloscope (strain gage).Cardiac output was determined by the Fick principle3 in five of the acute studies and by the T-1824 dilution method4 in the other five. The latter procedure was employed in all cases of long-term administration. Cardiac index was calculated per square meter of body surface.

IT HAS BEEN PROVED that the administration of chlorothiazide reduces blood pressure in hypertensive patients but not in lormotensive ones' and also that this drug affects renal hemodynamics in patients with essential hypertension.2 3 In order to determine whether there is a relationship between changes in renal hemodynamics and variations in blood pressure, a comparative study was made on the action of chlorothiazide in normotensive and hypertensive subjects.Material and Methods Eight normotensive subjects and 10 patients with early essential hypertension were studied. All hypertensive subjects were at rest and on lowsalt diet and placebo. Basal and casual blood pressure readings were taken daily and after these were stabilized the study was begun.Mean arterial blood pressure was calculated in all cases on the basis of the sum of the diastolic pressure plus one third of the pulse pressure.Glomerular filtration rate (Cin) and renal plasma floW (CPAH) were measured in both groups and osmotic clearance (Cosm) determined in all normotensive and in seven hypertensive subjects.Free water clearance (CH,o) and free water reabsorption (TCH,o) were calculated upon the basis of osmotic clearance and urine flow (V).These determinations were made before, at 60 minutes and at 90 minutes after the intravenous administration of 500 mg. of chlorothiazide in normotensive and at 40 minutes and 70 minutes in hypertensive subjects. All values were corrected to 1.73 M.2 of body surface.All normotensive and two hypertensive subjects (E.O. and S.P.) were overhydrated.Inuline was determined by a modification of Harrison's method,4 para-aminohippurate by the Smith et al. method,5 and osmolarity by the Fiske osmometer.

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The renal function, including sodium excretion rates, were studied in 27 patients with early essential hypertension, before and during angiotensin infusions. The patients had a preparatory period of salt loading for four days taking a supplement of 7 g of NaCl. Determinations were made during two 30-minute periods before the angiotensin and for two 30-minute periods afterward. Arterial blood pressure was increased in all 27 patients and renal plasma flow decreased in 25. The glomerular filtration rate changes were not statistically significant, showing some increase in 15 and a decrease in 11 patients. When the group was divided into those in which there was a decrease in sodium excretion (11 patients), and those in which there was an increase in sodium excretion (16 patients), with angiotensin infusion, a correlation with the control blood pressure was evident. The patients in whom an increase occurred had a control mean blood pressure greater than 136 mm Hg, and those exhibiting a decrease of sodium excretion, a blood pressure less than 136 mm Hg. Salt excretion did not correlate with the increment in blood pressure or renal resistance changes. The minor changes in glomerular filtration of sodium of the two groups could not explain the different excretory patterns which are attributed to an alteration of the tubular transport of sodium.