Type 2 angiotensin II receptor is downregulated in cardiomyocytes of patients with heart failure

Background: The human heart expresses type 2 angiotensin (AT(2)) receptor, but the function is poorly defined. Methods: In the present study, we inves tigated (1) the cellular localization of the AT(2) receptor and (2) the rel ationship between the AT(2) receptor protein expression and the cardiac fun ction of patients with ischemic heart disease. The receptor localization wa s assessed by immunohistochemistry and the protein expression was quantifie d by Western blotting in atrial tissues freshly obtained from 22 patients u ndergoing coronary artery bypass graft surgery (63.0+/-11.0 years old; male ratio, 85%). Prior to the surgery, blood was drawn for determination of at rial-natriuretic hormone level and the left ventricular function was assess ed by ultrasound cardiography. Results: The results of immunohistochemistry showed that the AT(2) receptor was localized to cardiomyocytes and was not present in fibroblasts, vascular smooth muscles, or vascular endothelium. Atrial tissues showed various degrees of structural remodeling, but the loc alization of the AT(2) receptor was nor altered in any tissue sections. The amount of the AT(2) receptor was negatively correlated with end-diastolic left ventricular diastolic dimension (r=-0.56, P<0.01), calculated left ven tricular mass index (r=-0.51, P<0.02) and the plasma atrial natriuretic pep tide (ANP) concentration (r=-0.62, P<0.01) and positively correlated with l eft ventricular ejection fraction (r=0.48, P<0.05). Conclusions: (1)The AT( 2) receptor is localized to cardiomyocytes independently of the cardiac fun ction. (2) Left ventricular dysfunction is associated with decreased expres sion of myocardial AT(2) receptor protein. (C) 2000 Elsevier Science B.V. A ll rights reserved.