Enalapril and Lisinopril in Renovascular Hypertension Antihypertensne and Hormonal Effects of Two New Angio-Tensin-Converting-Enzyme (ACE) Inhibitors

Abstract

We assessed the antihypertensive and hormonal effects of two new angiotensin converting enzyme (ACE) inhibitors. enalapril (MK-421) and lisinopril (MK-521) in 22 patients with renovascular hypertension. All patients had angiographically verified renal artery lesions, 3 had bilateral renal artery stenosis and one a stenosis in a single kidney, and the rest had unilateral renal artery stenosis. After placebo treatment for 3 days in hospital, increasing doses from 5 to 40 mg daily, of both ACE-inhibitors were given. Both drugs induced a significant fall in blood pressure (BP). Significant BP reductions were seen after 2 h with a maximum fall for the enalapril group at a dose of 40 mg 4 h after drug intake (mean supine BP decrease-31/24 mm Hg, standing-29/16 mmHg). The corresponding maximal BP reductions were for the lisinopril group at a dose of 40 mg o.d. at 6 h: mean supine BP fall-25/28 mmHg and standing-33/31 mm Hg. Both drugs significantly inhibited serum ACE to about 5 to 10% of initial values and with a duration for more than 24 h. Both drugs also caused a decrease in plasma All levels and also in plasma aldosterone concentrations. There were no toxic effects and no serious side effects. Careful monitoring of biochemical variables showed no significant changes. We conclude that both enalapril and lisinopril are effective and very Safe agents for the treatment of renovascular hypertension and with a long duration of action and with very good tolerance.

Pharmacokinetics of lisinopril (IV/PO) in healthy volunteers

“…The subjects drank 150 ml of tap water at regular intervals from 1 h before drug until 14 h post-drug administration to ensure adequate urine output. Blood samples for drug assay were collected without heparin at 0 (predrug), 10, 20, and 30 min, and at 1, 1.5, 2,4,6,8,12,24,36,48,60, and 72 h. Urine was collected in fractions at -1 to 0 (pre-drug), 0 to 2,2 to 4,4 to 8,8 to 12, 12 to 24, 24 to 36, 36 to 48, 48 to 72, 72 to 96, and 96 to 120h. Blood was collected into nonsiliconized, plain glass tubes, allowed to clot at room temperature, the tubes then 'rimmed' and refrigerated.…”

The Importance of Renin‐angiotensin Blockade in Patients With Cardio‐renal Disease

“…The first of these, captopril, was designed based on known inhibitors of another zinc‐containing metalloprotease, carboxypeptidase A and included a sulphydryl‐containing amino acid to serve as the ligand for the zinc moiety (Rubin et al 1978). This was soon followed by the development of many of the ACE inhibitors frequently used today (Ferguson et al 1982; Millar et al 1982; Karlberg et al 1984; Xiang et al 1985; Klutchko et al 1986; Richer et al 1986).…”

Mammalian Peptide Hormones: Biosynthesis and Inhibition

“…Many inhibitory substances followed, including enalaprilat [195] and lisinopril [196]. These and a variety of further ACE inhibitors with their respective structures have been reviewed by Nemec et al [189].…”