Why Do Thiazide Diuretics Lower Blood Pressure in Essential Hypertension?

Abstract

This review must have an aura of apology about it, since it does not deliver the genuine nugget which is our goal. Oral diuretics, such as the thiazides or chlorthalidone, will indubitably lower the blood pressure of most patients with essential hypertension (1, 2). There are more than a hun dred medical articles attesting to this. Since the author treats hypertensive patients, he can abundantly confirm these reports. In moderately large doses, these drugs by themselves will drop the blood pressure of most patients with primary hypertension. Furthermore, these drugs enhance the antihyperten sive effect of all other hypotensive drugs. In this review an attempt will be made to explain this important drug effect, but the ultimate explanation is still lacking (hence, the apology).The pure effect of these drugs can best be brought out when they are used alone. If the diuretic agents are taken daily by mouth at a dose level which produces a half maximal or three-fourths maximal diuresis, the blood pressure of hypertensive patients gradually begins to drop, and after two weeks it is often 30 mm lower in systolic pressure and 20 mm lower in diastolic pressure. With continued administration of the drug, the blood pressure is maintained at the lower level almost indefinitely. Very little tolerance to the drug is seen. Additional antihypertensive drugs can be sub sequently added to the regimen and their effect is enhanced in the presence of the thiazide medication.When the thiazides are first administered, they have their usual diuretic action and there is an increased excretion of sodium and water. In some parts of the renal tubule, there is a diminished reabsorption of filtered so dium and water, which leads to the diuresis. The mechanism here is in dis pute. Dirks et al. (3) have noted in micropuncture studies of dog kidney that inulin concentrations in proximal tubular fluid are the same in thiazide treated dogs as in non treated controls. This would suggest that the actual "diuresis" is not occurring in the proximal convoluted tubule. On the other hand, Ullrich (4), using the split-oil-droplet technique in micropuncture studies, finds that thiazide diuretics greatly diminish the reabsorption of sodium and water from segments of proximal convoluted tubule. There is a way to reconcile partially these seemingly opposite views. It is quite possible

The Neurogenic Component in the Experimental Hypertensive Rat

“…Furthermore, H44/68 had no significant hypotensive action unless used in doses reported to produce almost complete depletion of cate cholamines in heart tissue [11]. The hypotensive effects of frusemide were similar to those obtained using thiazide diuretics [26], However, diazoxide, a thiazide derivative with no diuretic action, is a potent hypotensive agent in hypertensive animals [20].…”

Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics

“…One long-standing indirect vasodilation hypothesis is reverse whole-body regulation [33]. Specifically, this hypothesis states that blood vessels adapt to the initial thiazide-induced plasma volume loss and decrease in cardiac output by constricting [33]. Then, over time, vessels dilate to increase cardiac output back toward baseline levels [33].…”

“…Specifically, this hypothesis states that blood vessels adapt to the initial thiazide-induced plasma volume loss and decrease in cardiac output by constricting [33]. Then, over time, vessels dilate to increase cardiac output back toward baseline levels [33]. According to this hypothesis, the thiazide-induced vasodilation would originate from sodium-induced fluid loss, via inhibition of the NCC.…”

Urinary kallikrein activity and renal vascular resistance in the antihypertensive response to thiazide diuretics.

“…1 Proposed mechanisms for thiazide action in hypertension have included: 1) intravascular volume depletion secondary to its natriuretic action 1 …”