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Contribution of bradykinin to the cardioprotective effects of ACE inhibitors

L. Murphey1,1, D. Vaughan2,3 and N. Brown1

a Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
b Division of Cardiovascular Medicine, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
c Veterans Affairs Medical Center, Nashville, Tennessee, USA

1 Laine J. Murphey, MD, PhD, 556A Robinson Research Building, Vanderbilt University Medical Center, Nashville, TN 37232-6602, USA

Abstract

Bradykinin, through its B2 receptor, stimulates endothelial release of a number of vasodilators, such as nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). Angiotensin-converting enzyme (ACE) inhibitors enhance the effects of local bradykinin by decreasing its degradation and by increasing B2 receptor sensitivity. Clinical and experimental studies demonstrate that blockade of the B2 receptor attenuates the antihypertensive, antihypertrophic, and antiatherosclerotic effects of ACE inhibitors. Thus, the evidence strongly supports a role for bradykinin in mediating the cardiovascular benefits of ACE inhibitors.

Key Words: ACE inhibitors • ramipril • bradykinin • endothelial dysfunction • kallikrein-kinin system • renin-angiotensin system

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