Angiotensin converting enzyme inhibition improves coronary flow mediated vasodilation

In patients with coronary artery disease, endothelial dysfunction impairs coronary vasodilation during conditions of increased myocardial oxygen demand. Angiotensin converting enzyme inhibitors prevent bradykinin (BK) degradation which may improve endothelial function. The aim of our study was to assess the effect of intracoronary enalaprilat (EN) on flow mediated epicardial, and metabolic microvascular dilation produced by cardiac pacing. Furthermore, we assessed whether any observed improvement in vasomotion with EN was mediated by BK. We studied 19 patients, 17 of whom had mild coronary atherosclerosis or its risk factors. Quantitative angiography was used to measure epicardial coronary diameter (D) and a Doppler wire to measure blood flow velocity. Pacing decreased coronary vascular resistance (CVR) (-27 ± 16%, p< 0.001) and increased D (3.7 ± 9%, p = 0.056). EN (20 μg/min) produced no change in coronary haemodynamics. However, EN abolished abnormal flow-mediated epicardial constriction in segments which initially constricted with pacing alone (n = 20), whereas segments that dilated remained unchanged (n = 30). In the constricting epicardial segments, BK (62.5 ng/min) at a dose which did not alter baseline diameter, also abolished abnormal pacing induced constriction. In contrast, EN did not improve microvascular dilation in patients with or without depressed pacing induced dilation. These data suggest that EN, by increasing endogenous BK, improves flow mediated epicardial vasodilation in segments with endothelial dysfunction. The lack of effect of EN in the microcirculation may be because the endothelium contributes less to metabolic microvascular vasodilation than to flow mediated epicardial vasodilation. Baseline Pace Pace+EN Pace+BK Segments Diameter (mm) Dilating 2.01 ± 0.52 2.21±0.61 2.15±0.60 2.21±0.57 Constricting 2.13±0.65 2.02±0.62 2.15±0.66* 2.21±0.63** mean ± SD; *Pace v Pace+EN, p<0.005; **Pace v Pace+BK, p<0.001.