Time Course of Changes in Blood Pressure, Aldosterone and Body Fluids During Enalapril Treatment: A Double‐blind Randomized Study vs Hydrochlorothiazide Plus Propranolol in Essential Hypertension

Abstract

Aldosterone suppression is said to play a major role in the long term hypotensive efficacy of angiotensin converting enzyme inhibitors. However, in previous reports from other laboratories, plasma volume has been found mostly increased and sodium balance sometimes positive. The effects of the angiotensin converting enzyme inhibitor enalapril (10-40 mg/day, p.o., for 6 weeks) on blood pressure, body fluid volumes, renal function and plasma aldosterone were compared to those of hydrochlorothiazide (50 mg/day, p.o.) alone for 2 weeks and in association with propranolol (80-160 mg/day, p.o.) for 4 more weeks during a randomized double-blind parallel study in 14 essential hypertensives. Hydrochlorothiazide alone and in combination with propranolol induced slight and not significant change in either blood pressure and body fluids. The maximum hypotensive response to enalapril was achieved only after 2 weeks of continuous treatment possibly because after 1 week the hypotensive efficacy was lessened by a significant (P less than 0.05) fluid retention secondary to a transient and not significant fall in renal perfusion. At this time aldosterone was not significantly changed compared to pretreatment values. After 6 weeks on enalapril, blood pressure was significantly reduced, plasma aldosterone further but not significantly decreased and extracellular fluid volume was normal. These findings indicate that aldosterone suppression contributes to the blood pressure lowering effect of enalapril by offsetting the salt and water retention observed on starting treatment and due to direct vasodilation.

Angiotensin-Converting Enzyme Inhibitors

“…ACE‐1 is present in abundance in human glomeruli, 6 allowing renin‐dependent variations in the rate of generation of Ang II, which, in turn, modulate renal vascular resistance, efferent arteriolar tone, and glomerular filtration pressure. ACE‐1 inhibitors reduce adrenal aldosterone release in response to acute stimuli such as posture or salt‐depletion 7 but have little effect on plasma aldosterone chronically 8 . A more comprehensive explanation of the BP‐lowering effects of ACE inhibitors is offered by extensive observations that the brain and the cerebral vasculature respond to both local and systemic RAS systems.…”

Fluid Matters in Choosing Antihypertensive Therapy: A Hypothesis That the Data Speak Volumes

“…[82][83][84] Enalapril has been shown to cause transient increases in interstitial fluid volume after 1 week of administration, but these increases are short-lived, and extracellular fluid volume returns to baseline after 6 weeks of therapy. 85 Other studies have demonstrated that changes in body weight, extracellular fluid, and plasma volume are minimal with ACEIs. 86,87 Most studies have reported a low prevalence of edema in subjects treated with an ACEI.…”