Expression of cardiac angiotensin II AT₁ receptor genes in rat hearts is regulated by steroids but not by angiotensin II

Abstract

Objective: 

To examine the regulation by angiotensin II and by steroids of the expression of the angiotensin II AT_1a and AT_1b receptor genes 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 the AT₁ receptor antagonist losartan (40 mg/kg per day) or the angiotensin converting enzyme inhibitor ramipril (8 mg/kg per day). Circulating levels of glucocorticoids were elevated by subcutaneous injections of dexamethasone (400 μg/kg per day) and levels of mineralocorticoids were increased by subcutaneous injections of deoxycorticosterone acetate (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 clipping led to a 30% decrease in AT_1a mRNA, whereas treatment with frusemide, losartan or ramipril had no effect on the AT_1a or AT_1b mRNA levels. Rats fed a low-sodium diet showed a 37% increase in AT_1a gene 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 present 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, because glucocorticoids stimulate AT₁ receptor gene expression and mineralocorticoids inhibit it.