Bradykinin B 2 Receptor Antagonism Attenuates Blood Pressure Response to Acute Angiotensin-Converting Enzyme Inhibition in Normal Men

Abstract

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.