Similar effects of hydrochlorothiazide and spironolactone on plasma renin activity in essential hypertension
Sergio Acchiardo, M.D.
Harriet P. Dustan, M.D.
Robert C. Tarazi, M.D.
Thiazide diuretics are the most frequently used antihypertensive drugs. They reduce arterial pressure when used alone and enhance the effectiveness of nondiuretic antihypertensive drugs when used in combination. They cause sustained reductions of plasma volume (PV) and elevate plasma renin activity (PRA).1 Spironolactone, an aldosterone antagonist, produces similar effects on arterial pressure,2, 3 plasma volume,4 and plasma renin.5, 6 Of the possible causes of this hyperreninemia, chronic oligemia seemed most likely to play a major role, because we had found an inverse relationship between PV and PRA in normal men, in men with untreated essential hypertension, and in patients with untreated renovascular hypertension.7 However, treatment could bring other factors into play, such as decreases in arterial pressure,8, 9 decreases of plasma sodium,10 and modification of plasma potassium concentration.11, 12 In addition, the possibility of a direct effect of these drugs on the juxtaglomerular apparatus should be considered, because renin release evoked by furosemide has been attributed partly to inhibition of sodium transport by macula densa cells.13 Such a mechanism is not so readily accepted in explanation for elevation of PRA produced by spironolactone, because this drug is a potassium-sparing agent,14 and may have its major renal effects on tubular cells distal to the macula densa, although there is evidence to suggest that it also affects proximal portions of the nephron.15
A group of hypertensive patients treated with hydrochlorothiazide alone and another treated only with spironolactone provided an opportunity to study the effects of these two diuretics on PRA in regard . . .