Non-sulfhydryl-containing angiotensin-converting enzyme inhibitor (MK421): evidence for role of renin system in normotensive subjects.

Abstract

A non-sulfhydryl-containing inhibitor of angiotensin-converting enzyme (MK421) was given as a single dose in a randomised double-blind cross-over trial using 20 mg and 5 mg of MK-421 or matched placebo to nine normotensive volunteers receiving a sodium intake of 150 mmol (mEq) daily. The two dosages of MK-421 caused similar, significant falls in supine and standing blood pressure, which were maximum four to six hours after dosing (9.5-11.0% fall). With this fall in blood pressure there was a significant fall in activity of angiotensin-converting enzyme and in concentrations of plasma angiotensin II and aldosterone and a rise in plasma renin activity. Placebo caused no significant change in blood pressure or blood measurements. The study showed that MK-421 inhibits angiotensin-converting enzyme activity and lowers blood pressure in normotensive subjects. It strongly suggested that the renin system plays an important part in maintaining blood pressure in normotensive subjects receiving normal sodium intake. The results also suggest that this non-sulfhydryl-containing converting-enzyme inhibitor will be an effective blood-pressure-lowering drug in patients with blood pressure. A single dose of 5 mg was as effective at lowering blood pressure as a single dose of 20 mg.