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.
Recently, it has been shown that significant differences in hmmodynamic behaviour and electrolyte excretion exist between one kidney and the other early in the course of essential hypertension . The possibility has been considered that these differences are indicative of an intrinsic renal disturbance that could be responsible for the hypertensive process.The purpose of this study was to investigate whether or not these differences could be modified by a drug, such as chlorothiazide, which, besides its antihypertensive action, has a direct effect upon renal function. MATERIAL AND METHODSTen patients with essential hypertension were studied: 7 were at an early stage, as judged by the relatively minor renal functional impairment, and 3 had moderate kidney damage. In addition to the clinical diagnosis of essential hypertension, intravenous urograms were made and no evidence of disparity in renal size or function was found. Subsequently, the index proposed by Rapoport (1960) was calculated and gave values from 076 to 149.All patients were at rest, on low salt diet, normal fluid intake, and placebo. Blood pressure was taken under basal conditions and when stabilized, i.e. within 6 to 13 days, the study was begun.The patients were catheterized to 15 cm. above the ureteral meatus using 7F and 8F catheters in order to collect urine from each kidney. Another catheter was placed in the bladder to detect leakage around the ureteral catheters. Those patients in whom urine was found in the bladder were excluded from this study.Fifteen minutes after catheterization the renal function studies were begun. After injection of priming doses of inulin and p-aminohippurate, a sustaining infusion of these substances dissolved in 5 per cent glucose was administered at a constant rate of 1 ml. per minute by means of a Bowman pump.Urine and blood samples were taken during two periods totalling 60 minutes for determination of glomerular filtration rate (C1n), renal plasma flow (CPAH), and water and sodium excretion.In all 500 mg. chlorothiazide was administered intravenously, and urine and repeat blood samples were collected during two periods in 60 minutes.Inulin was determined by a modification of Harrison's method (Goldring and Chasis, 1944), and p-aminohippurate by the method of Smith et al. (1945). Sodium was determined in a Baird flame photometer.In the control period, as well as after the administration of chlorothiazide, readings of the arterial blood pressure were taken every five minutes. The average of these was used to calculate the mean arterial blood pressure which was considered as the sum of diastolic pressure plus one-third of pulse pressure.The percentage differences between the two kidneys were calculated by dividing the difference between them by their mean value. 325 on 11 May 2018 by guest. Protected by copyright.
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