Insertion-deletion polymorphism of the ACE gene modulates reversibility ofendothelial dysfunction with ACE inhibition

Background-The aim of this study was to examine whether angiotensin-convert ing enzyme (ACE) inhibition improves coronary endothelial dysfunction in pa tients with atherosclerosis and its risk factors and whether this was relat ed to the ACE insertion-deletion (I/D) polymorphism. Methods and Results-In 56 patients with atherosclerosis or its risk factors , we studied endothelium-dependent responses with acetylcholine and endothe lium-independent function with sodium nitroprusside, before and after ACE i nhibition with enalaprilat. Enalaprilat did not alter either resting corona ry tone or vasodilation with sodium nitroprusside. However, it potentiated the coronary microvascular and epicardial responses with acetylcholine; cor onary blood flow increased from 82 +/- 7 to 90 +/- 8 mL/min (P=0.05) after enalaprilat. Patients with depressed endothelial function (P<0.001) and tho se with ACE DD or ID genotypes (P=0.002) but not those homozygous for the I allele had the greatest improvement by multivariate analysis. Similarly, a cetylcholine-mediated epicardial vasomotion improved in segments that initi ally constricted (endothelial dysfunction): from - 10.1 +/- 1% to -1.4 +/- 2% (P<0.001) after enalaprilat. No augmentation was observed in segments th at dilated (normal endothelial dysfunction) with acetylcholine. Patients wi th the D allele, hypercholesterolemia, and smokers (all P<0.05) had greater improvement. Conclusions-Acute ACE inhibition improves coronary epicardial and microvasc ular endothelium-dependent vasomotion in patients with atherosclerosis or i ts risk factors who have endothelial dysfunction and presence of the D alle le.