Duration of action and short-term hormonal responses to enalapril (MK 421) in normal subjects

Enalapril is a converting enzyme inhibitor with a prolonged duration of action. We investigated the arterial pressure and hormonal responses to angiotensin I infusion(s) in eight normotensive human volunteers at various intervals after administration of 10 mg enalapril to assess more precisely its duration of action, particularly in relationship to angiotensin II's influence on aldosterone secretion and renal vasoconstriction. In normotensive sodium-restricted subjects, there was significant attenuation (p less than 0.025) of diastolic blood pressure response to angiotensin I infusion even as long as 28 h after administration of enalapril. This was accompanied by a significant (p less than 0.02) accumulation of angiotensin I and reduction of the angiotensin II increment in response to angiotensin I infusion. In contrast to the persistent efficacy of enalapril, as assessed by angiotensin I infusion, basal levels of angiotension II had returned to control levels by 22-24 h postdrug. Yet there was a persistent reduction of diastolic blood pressure even as long as 28 h postdrug. The persistent hypotension could not be explained on the basis of changes in other potential vasoactive factors (epinephrine, norepinephrine, bradykinin, or prostaglandin), as none of these was significantly modified by enalapril administration. In summary, enalapril in a dose of 10 mg p.o. produced a significant reduction in blood pressure in this study for up to 28 h. Unlike captopril, enalapril does not modify circulating prostaglandins and kinins. Although the level of activation of the renin-angiotensin system had returned to control values 24 h after enalapril administration, there was evidence from the angiotensin I infusions of continued blockade of the angiotensin-converting enzyme for as long as 28 h.