EXPRESSION OF CARDIAC ANGIOTENSIN-II AT(1) RECEPTOR GENES IN RAT HEARTS IS REGULATED BY STEROIDS BUT NOT BY ANGIOTENSIN-II

Objective: To examine the regulation by angiotensin II and by steroids of the expression of the angiotensin II AT(1a) and AT(1b) receptor ge nes in rat hearts. Methods: Endogenous levels of angiotensin II in the rats were increased either by unilateral 0.2-mm renal artery clips or by subcutaneous infusions of frusemide (12 mg/day) and by low-sodium diet. To inhibit endogenous angiotensin II actions the rats received t he AT(1) receptor antagonist losartan (40mg/kg per day) or the angiote nsin converting enzyme inhibitor ramipril (8 mg/kg per day). Circulati ng levels of glucocorticoids were elevated by subcutaneous injections of dexamethasone (400 mu g/kg per day) and levels of mineralocorticoid s were increased by subcutaneous injections of deoxycorticosterone ace tate (2 mg/kg per day). AT(1a) and AT(1b) messenger RNA (mRNA) levels were semiquantified by reverse-transcriptase polymerase chain reaction and related to actin mRNA. Results: The AT(1a) mRNA:AT(1b) mRNA ratio in the hearts of untreated rats was 10:1. Unilateral renal artery cli pping led to a 30% decrease in AT(1a) mRNA, whereas treatment with fru semide, losartan or ramipril had no effect on the AT(1a) or AT(1b) mRN A levels. Rats fed a low-sodium diet showed a 37% increase in AT(1a) g ene expression. Dexamethasone increased AT(1a) mRNA by 100% and AT(1b) mRNA by 300%, whereas deoxycorticosterone acetate treatment decreased AT(1a) mRNA levels to 30% of the control values. Conclusions: The pre sent results suggest that the expression of the predominant cardiac AT (1a) receptor gene is not feedback-regulated by endogenous angiotensin II, whereas steroid hormones appear to be effective regulators, becau se glucocorticoids stimulate AT(1) receptor gene expression and minera locorticoids inhibit it.