Increased tissue angiotensin-converting enzyme activity impairs bradykinin-induced dilation of coronary arterioles in obesity

Attila Feher, James Cassuto, Andras Szabo, Vijay Patel, M. Vinayak Kamath, Zsolt Bagi

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Background: Bradykinin (BK) is a key mediator regulating coronary blood flow. It is degraded by angiotensin-converting enzyme (ACE), but what is unknown is whether enhanced tissue ACE activity interferes with BK-induced coronary vasodilation in obesity. Methods and Results: Coronary arterioles (~100μm) were isolated from rats on a normal or high-fat diet (HFD) and from lean or obese patients undergoing heart surgery (n=74). We found that BK-induced dilation was diminished in the coronary arterioles of HFD rats, when compared with controls. When administered in vitro, the ACE inhibitor, captopril, restored the coronary dilation response to BK in HFD rats, but did not affect control responses. Abundant ACE expression was detected in coronary endothelium, which was associated with increased ACE activity in HFD arterioles, as measured by increased response to the ACE substrate, angiotensin I. Moreover, we found that in the coronary arterioles of obese patients, BK-induced dilation was augmented by in vitro captopril administration. Correspondingly, ACE activity was increased in the coronary arterioles of obese patients when compared with the non-obese. Logistic regression analysis revealed that obese patients taking ACE inhibitors prior to surgery exhibited an enhanced dilation response to BK. Conclusions: We demonstrated augmented tissue ACE activity in the coronary arterioles of obese subjects, which leads to reduced coronary dilation response to BK. We provide a rationale for ACE inhibitor therapy in obese patients to improve dilatation of coronary microvessels. (Circ J 2013; 77: 1867-1876).

Original languageEnglish (US)
Pages (from-to)1867-1876
Number of pages10
JournalCirculation Journal
Volume77
Issue number7
DOIs
Publication statusPublished - Jul 1 2013

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Keywords

  • Angiotensin-converting enzyme
  • Bradykinin
  • Coronary microcirculation
  • Obesity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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