THE ANGIOTENSIN-II TYPE-1 RECEPTOR GENE POLYMORPHISM IS ASSOCIATED WITH CORONARY-ARTERY VASOCONSTRICTION

Objectives. This study sought to assess the potential association of t he angiotensin-converting enzyme (ACE) and angiotensin II type 1 (AT1) receptor gene polymorphisms on coronary vasomotion in humans. Backgro und Abnormal coronary vasomotion plays a role in the clinical expressi on of coronary atherosclerosis. The components of the renin-angiotensi n system are important determinants of vasomotor tone, Furthermore, ep idemiologic evidence suggests that these components are involved in th e pathogenesis of coronary artery disease. Indeed, two genetic polymor phisms of the ACE and AT1 receptor genes were synergistically associat ed with the occurrence of myocardial infarction. The influence of thes e genetic polymorphisms on the risk of myocardial infarction may be re lated, at least in part, to a deleterious effect on coronary vasomotio n. Methods. We studied the response of angiographically normal human c oronary arteries after intravenous injection of methylergonovine malea te, a potent vasoconstrictor whose effects have been previously explor ed in various aspects of coronary artery disease. We characterized the ACE and AT1 receptor genotypes in a consecutive series of 140 patient s with normal coronary arteries, Coronary vasomotion was assessed with quantitative coronary angiography. Results. No effect of the ACE gene polymorphism was detected. Conversely, the patients carrying the AT1 receptor CC genotype (n = 13) had significantly greater vasoconstricti on in distal coronary vessels (p < 0.009). Conclusions. The AT1 recept or gene polymorphism is associated with coronary vasomotion in humans. (C) 1997 by the American College of Cardiology.