Use of the converting enzyme inhibitor enalapril in renovascular hypertension. Effect on blood pressure, renal function, and the renin-angiotensin-aldosterone system.

Abstract

Thirteen patients were entered into a protocol to assess the safety and efficacy of enalapril (MK 421), 5 to 20 mg b.i.d., and hydrochlorothiazide, 50 to 100 mg daily, for the treatment of renovascular hypertension. Specifically monitored were the effects of therapy on blood pressure and pulse, renal function, and the renln-angiotensin-aldosterone axis. Enalapril and hydrochlorothia-zide therapy produced excellent control of blood pressure with no adverse side effects. After approximately 8 weeks of therapy, renal vascular resistance was decreased and no adverse effects on glomeru-lar filtration rate or renal blood flow were noted, except in one patient with a functional unilateral stenotic kidney. Patients receiving enalapril and hydrochlorothiazide showed stimulation of plasma renin activity and suppression of plasma angiotensin II, although the initial degree of suppression was not sustained in all patients during prolonged therapy. Although plasma aldosterone concentration was initially suppressed, the degree of suppression was not sustained. Nine patients have been followed for an additional 6 months; none have experienced further progression of renal disease, as assessed by repeated measurements of glomenilar filtration and effective renal plasma flow. These results suggest that combined enalapril and hydrochlorothiazide therapy is safe and effective in the medical management of renovascular hypertension and that blood pressure control may be achieved in the absence of sustained interruption of the renin-angiotensin-aldosterone system. (Hypertension 8: 290-297,1986) KEY WORDS • glomerular filtration aldosterone system renal plasma blood flow • renin-angiotensin-T HAT the converting enzyme inhibitors capto-pril 1-3 and enalapril (MK 421) 6 " 9 effectively lower blood pressure in patients with renovas-cular hypertension has been demonstrated repeatedly. The initial fall in arterial pressure appears to be proportional to the concurrent fall in plasma angiotensin II concentration for both drugs. '• 7 Since the renin-angio-tensin system plays a crucial part in the regulation of glomerular filtration rate when renal perfusion pressure is low, and short-term administration of a converting enzyme inhibitor destroys the integrity of this system , administration of a converting enzyme inhibitor to a patient with renovascular hypertension carries the risk of precipitating serious renal dysfunction. Indeed,

Increase in Serum Total Angiotensin‐converting Enzyme Activity With Enalapril Therapy in Humans: A Controlled Trial

“…A fall in plasma A11 concentrations might be expected to result from decreased A1 to A11 conversion in circulating blood consequent upon decreased serum free ACE after enalapril treatment. That such a fall was not observed in this study, nor in some others (Reams et al 1986;Mento & Wilkes 1987), has been attributed to direct and negative feedback effects of ACE inhibition. Administration of captopril, another ACE inhibitor, has been shown to increase renin mRNA in kidney (Iwai et al 1988) which, together with the removal of the inhibitory effect of A11 on renin release, results in increases in plasma renin and A1 concentrations.…”

“…Acute administration of enalapril causes falls in plasma angiotensin 11 (AII) and aldosterone concentrations, and increases in plasma renin activity (PRA) and angiotensin I (AI) concentration (Hodsman et al 1984). However, chronic administration in humans has been reported to cause no sustained suppression of plasma A11 or aldosterone concentration (Reams et al 1986); in the rat, plasma A11 may increase above normal during chronic enalapril treatment (Mento & Wilkes 1987 lack of continued A11 suppression is induction of ACE production. Studies in the rat have shown that lisinopril administered orally for 2 weeks decreased free ACE in plasma and several tissues, but increased total ACE in plasma and lung (Kohzuki ef al.…”

Effects of Angiotensin-Converting Enzyme Inhibition versus Conventional Antihypertensive Therapy on the Glomerular Filtration Rate

“…Such findings have also been reported in smaller studies of nondiabetic patients with hyperten sion [7,8],…”

Chronic Kidney Disease in Diabetes

“…Drugs that block the RAAS reduce intraglomerular pressure which, in turn, leads to a rise in serum creatinine of up to 30% which then stabilizes (110). Although these drugs can be used safely in people with ischemic nephropathy, these people may have an even larger rise in serum creatinine when these drugs are used (111)(112)(113). In the case of severe renal artery stenosis that is bilateral (or unilateral in a person with a single functioning kidney), RAAS blockade can precipitate renal failure.…”