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(Circulation. 1999;100:2305.)
© 1999 American Heart Association, Inc.

Editorials

Bradykinin in the Heart

Friend Or Foe?

Louis J. Dell’Italia, MD; Suzanne Oparil, MD

From the University of Alabama, Department of Medicine, Vascular Biology and Hypertension Program, Division of Cardiovascular Disease and the Birmingham Veterans Affairs Medical Center, University Station, Birmingham, Ala.

Key Words: Editorials • bradykinin • angiotensin • myocardium • heart failure • hypertension

Hypertension and heart failure are marked by activation of both the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. These forms of neurohumoral activation, in turn, have deleterious effects on the heart, kidney, and other target organs, worsening the prognosis in these disease states. Pharmacological agents that interrupt the RAAS are useful in both improving hemodynamics and preventing morbidity and mortality in such patients. In particular, treatment with ACE inhibitors has been shown to improve survival in patients with advanced heart failure and after myocardial infarction. It is hypothesized that ACE inhibitors exert beneficial effects by inhibiting both circulating and cardiac tissue ACE, thus attenuating unfavorable remodeling of the left ventricle (LV), reducing afterload, and improving the balance between thrombotic and thrombolytic factors. It remains unclear whether the dominant mechanism of action of ACE inhibitors in the setting of LV dysfunction relates to their global hemodynamic effects (which result in improved loading conditions), to reduced production of angiotensin (Ang) II with subsequent diminished Ang II type 1 (AT₁) receptor activation, or to alteration of other neurohormonal systems, such as the kallikrein-kinin system.

Importantly, in addition to generating Ang II from Ang I, ACE catalyzes the degradation of bradykinin (BK) to inactive metabolites.¹ Studies of recombinant full-length ACE have shown that the apparent K_m of ACE for BK is substantially lower than for Ang I, which indicates more favorable kinetics for hydrolysis of BK than for conversion of Ang I to Ang II.² Furthermore, site-directed mutagenesis demonstrated that the K_m . . . [Full Text of this Article]

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