Expression and localization of angiotensin subtype receptor proteins in the hypertensive rat heart

The cellular localization of the AT(2) receptor and the regulation of its e xpression in hypertrophied left ventricle are not well known. We compared t he expression of the cardiac AT(1) and AT(2) receptor in spontaneously hype rtensive rats/Izumo strain (SHR/Izm) and Wistar Kyoto rats/Izumo strain (WK Y/Izm), ages 4, 12, and 20 wk, by means of immunohistochemistry and Western blot analysis. In SHR/Izm, compared with WKY/Izm, blood pressure (161 +/- 2 vs. 120 +/- 2 mmHg at 12 wk, P less than or equal to 0.01, and 199 +/- 3 vs. 123 +/- 3 mmHg at 20 wk, P less than or equal to 0.01) and heart-to-bod y weight ratio (3.76 +/- 0.07 vs. 3.06 +/- 0.06 mg/g at 12 wk, P less than or equal to 0.01, and 3.90 +/- 0.08 vs. 3.01 +/- 0.12 mg/g at 20 wk, P less than or equal to 0.01) were significantly elevated. There was no differenc e in these values between the two strains at 4 wk of age. Histologically, 2 0-wk-old SHR/Izm demonstrated myocardial hypertrophy, a thickening of the s mooth muscle layer of the intracardiac arteries, and perivascular fibrosis. By immunohistochemistry, the AT(2) receptor was localized to cardiomyocyte s and vascular endothelial cells, but not in the vascular smooth muscle cel ls. No major AT(2) receptor signal was observed in perivascular fibrosis at any age in either strain of rats. No difference was detected in this local ization between the two strains. By Western blotting, a single 44-kDa band for the AT2 receptor and a single 60-kDa band for the AT(1) receptor were d etected in ventricles from both strains of rats at all ages. Densitometric analysis demonstrated that the AT(2) receptor 44-kDa band was decreased by 20% at 12 wk and 32% at 20 wk (P < 0.01) in SHR/Izm compared with WKY/Izm. The intensity of the AT(1) receptor 60-kDa band was increased by 57% in 20- wk-old SHR/Izm compared with WKY/Izm (P < 0.05). There was no significant d ifference in the intensity of the 44- or 60-kDa bands in 4-wk-old animals o f either strain. We demonstrated a decrease in the AT(2) receptor and an in crease in the AT(1) receptor protein with no change in their localizations in hypertrophied left ventricular myocytes of SHR/Izm.