Abstract 16453: Increased Activity of Tissue ACE Impairs Dilation of Coronary Arterioles in Obesity
Angiotensin converting enzyme (ACE) inhibitors prevent cardiovascular complications independent from their blood pressure lowering effect. We hypothesized that vascular ACE activity is increased in obesity, which has a significant impact on the regulation of coronary arteriolar diameter. In isolated, pressurized coronary arterioles (~ 100 µm) of obese rats (male Wistar rats fed a 60% fat containing diet for 12 weeks) bradykinin (BK) elicited vasoconstriction, whereas it dilated coronary arterioles of control animals (rats on normal diet). Incubation and in vitro presence of an ACE inhibitor, Captopril restored dilation to bradykinin in obese rats and did not affect the control response. Dilation to angiotensin I (Ang I) was significantly enhanced in arterioles of obese rats, which was diminished by Captopril in both groups. Ang II-induced dilations were not different between control and obese rats. In coronary arterioles protein expression of ACE was abundant in endothelial cells, which was increased in arteries from obese rats. Moreover, coronary arterioles were obtained from patients (N=67) undergoing heart surgery. In human coronary arterioles BK-induced dilation was augmented, whereas Ang I-induced dilation was reduced by Captopril, when administered in vitro. Prior ACE inhibitor therapy was associated with an enhanced BK-induced coronary dilation in lean and overweight, but not in obese (body mass index > 30) patients (2-way ANOVA). Collectively, we provide functional evidence for an augmented activity of ACE in coronary arterioles of obese subjects, which diminishes BK-induced vasodilation. We propose that ACE inhibitor therapy in obese patients does not correlate and may not sufficient to improve vasodilator function of coronary microvessels.
- © 2011 by American Heart Association, Inc.