The importance of plasma and extracellular fluid volumes in the mechanism of the antihypertensive effect of chlorothiazide is disputed. The present investigation indicates that the lowering of blood pressure is accompanied by reductions in plasma and extracellular fluid volumes and in body weight. Furthermore, re-expansion of plasma volume with salt-free dextran reverses the antihypertensive effect. However, since gradual reaccumulation of extracellular fluid occurs during 1 year of continuous treatment, the late antihypertensive effects of chlorothiazide cannot be explained by the volume-depletion mechanism.T HE discovery of the antihypertensive action of chlorothiazide" 2 raised certain questions as to its mechanism of action. These questions included (1) whether the hypotensive response was caused by salt depletion or by some independent factor; (2) if produced by salt loss, by what mechanism it reduced blood pressure; (3) the factors that lead to increased reactivity to other antihypertensive agents; and (4) the reason for the moderate antihypertensive action of the drug when used alone in hypertensive patients and the absence of such activity in normotensive subjects.3 4 Complete answers to these questions cannot yet be given. This report concerns an attempt to elucidate some of the factors involved.
MATERIALS AND METHODSTwenty male hypertensive patients with no symptoms or signs of congestive heart failure or edema were hospitalized and placed on a standard diet containing 1.5 Gm. of salt per day plus a supplement of 3 Gm. of salt in tablet form. This supplied a sodium intake of approximately 75 mEq. per day. Most of these patients were From the Veterans Administration Hospital and
Chlorothiazide was synthesized by Novello and Sprague' and found to be a potent, orally effective diuretic and saluretic agent by Beyer, Baer, RUSSO, and Haimbach.2 Ford, Moyer, and Spurr3 have reported on its diuretic and saluretic properties in patients with edema. Because of its pronounced saluretic action a clinical trial of this agent was undertaken in hypertensive patients.The present report covers our experience to date in 105 patients, 90 of whom were hypertensive. In the beginning our major interest was in the attempt to potentiate the action of other antihypertensive drugs. A summary of early results was submitted as an abstract to
Mild hypercalcaemia associated with primary hyperparathyroidism has been increasingly recognized with the use of automated biochemical screening. Management is often difficult as symptoms are often absent or non-specific. Accordingly, we employed the hypocalcaemic effect of the diphosphonate APD to assess the effect of an acute fall in plasma calcium on indices of general well being, blood pressure, and vasoactive hormones in patients with mild primary hyperparathyroidism. Ten patients were studied in a randomized single blind, placebo-controlled cross-over study, using 30 mg APD intravenously or control saline infusion, over 2 h. Metabolic measurements, formal tests of muscle strength and cognitive function, and a standardized questionnaire were assessed 7 days after infusions. Albumin corrected plasma calcium was significantly lower (mean 2.49 +/- 0.04 SEM mmol/l) after APD when compared to control values (2.70 +/- 0.06 mmol/l, P less than 0.001). Twenty-four-hour urinary calcium, plasma magnesium and absolute monocyte count decreased significantly, whereas plasma parathyroid hormone increased after APD (P less than 0.05). There was no significant change in hypercalcaemic symptoms, muscle strength or cognitive function, and blood pressure, renin, aldosterone and atrial natriuretic peptide did not change. Side-effects, when they occurred, were mild. It is concluded that APD is a safe and effective means of lowering plasma calcium in mild primary hyperparathyroidism, but these acute reductions are associated with little or no improvement in clinical status in these patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.