Enalapril (MK421) and its lysine analogue (MK521): a comparison of acute and chronic effects on blood pressure, renin-angiotensin system and sodium excretion in normal man.

The immediate and long-term effects of enalapril (MK421) and its lysine analogue (MK521) in once-daily dosage, were compared in a study of 12 normal subjects. Both compounds lowered blood pressure equally throughout 24 h without causing tachycardia. The biochemical changes with MK521 were more sustained than with MK421, but this did not affect the magnitude of blood pressure reduction. Twenty-four hours after the previous dose, with both active drugs, plasma renin concentration was significantly higher on day 8 than on day 1, though angiotensin I did not increase in proportion; this probably reflects a fall in renin-substrate with prolonged converting enzyme inhibition. There was an early natriuresis with each compound but this effect was no longer apparent after 8 days of continuous therapy. Both MK421 and MK521 were well tolerated with no serious side effects.