Bradykinin B(2) receptor antagonism attenuates blood pressure response to acute angiotensin-converting enzyme inhibition in normal men.

Abstract

The physiological effects of angiotensin-converting enzyme (ACE) inhibition may be in part mediated by bradykinin. We investigated the effect of coadministration of the specific bradykinin B(2) receptor antagonist icatibant on hemodynamic and neurohormonal responses to acute intravenous ACE inhibition in normal men on a normal sodium diet. We performed a 4-phase, double-blind, double-dummy, placebo-controlled study in 12 male volunteers. The bradykinin antagonist icatibant (10 mg IV) was coadministered over the first 15 minutes of a 2-hour infusion of the ACE inhibitor perindoprilat (1.5 mg IV). Perindoprilat inhibited ACE activity and elicited the expected changes in active renin concentration and angiotensin peptides. Over the 3 hours after the start of drug infusion, perindoprilat lowered and icatibant increased mean arterial blood pressure (each P<0.0005 versus placebo). Coadministration of icatibant attenuated the mean arterial blood pressure response to perindoprilat (P<0.0005) but had no effect on neurohormonal responses to perindoprilat. Our study indicates that the bradykinin B(2) receptor antagonist icatibant attenuates the short-term blood pressure-lowering effect of acute ACE inhibition in normal men on a normal sodium diet. Bradykinin B(2) receptor antagonism alone increases resting blood pressure. Bradykinin may be involved in the control of blood pressure in the resting state in humans.