AT 1 and AT 2 Angiotensin Receptor Gene Expression in Human Heart Failure

Abstract

Background The availability of selective antagonists for angiotensin II receptors has focused interest on the gene expression of angiotensin II–receptor subtypes in the human heart. Methods and Results We analyzed expression of the AT₁ and AT₂ subtypes of the angiotensin II receptor in ventricular myocardium taken from 9 donor hearts before implantation and from 12 patients with heart failure (6 with dilated cardiomyopathy and 6 with ischemic heart disease). Competitive reverse transcription–polymerase chain reaction with synthetic RNA internal standards was used to detect mRNA for both subtypes and to quantify relative differences in levels between failing and nonfailing ventricular myocardium. AT₁- and AT₂-receptor mRNA could be detected in all samples. AT₁-receptor gene expression was 2.5-fold greater in nonfailing hearts than in patients with failing hearts (P=.015). There was no significant difference in AT₂-receptor mRNA expression in failing and nonfailing hearts. Conclusions The level of expression of the angiotensin AT₁ receptor appears to decrease in the failing human ventricle whereas the level of AT₂ expression is unaffected. These changes parallel the changes found in human ventricular myocardium at the receptor level, suggesting that the changes in receptor level may result from changes in gene expression or mRNA stability.