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(Hypertension. 2000;36:132.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Bradykinin B₂ Receptor Antagonism Attenuates Blood Pressure Response to Acute Angiotensin-Converting Enzyme Inhibition in Normal Men

Iain B. Squire; Kevin P. J. O’Kane; Niall Anderson; John L. Reid

From the Department of Medicine & Therapeutics and the Robertson Centre for Biostatistics (N.A.), University of Glasgow, Glasgow, Scotland.

Correspondence to Dr Iain Squire, Department of Medicine & Therapeutics, University of Leicester, Clinical Sciences Building, Leicester LE2 7LX, UK. E-mail is11{at}le.ac.uk

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 B₂ 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 B₂ receptor antagonist icatibant attenuates the short-term blood pressure–lowering effect of acute ACE inhibition in normal men on a normal sodium diet. Bradykinin B₂ receptor antagonism alone increases resting blood pressure. Bradykinin may be involved in the control of blood pressure in the resting state in humans.

Key Words: blood pressure • angiotensin-converting enzyme • bradykinin • icatibant

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