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 AT1a and AT1b 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 micrograms/kg per day) and levels of mineralocorticoids were increased by subcutaneous injections of deoxycorticosterone acetate (2 mg/kg per day). AT1a and AT1b messenger RNA (mRNA) levels were semiquantified by reverse-transcriptase polymerase chain reaction and related to actin mRNA. RESULTS:The AT1a mRNA:AT1b mRNA ratio in the hearts of untreated rats was 10:1. Unilateral renal artery clipping led to a 30% decrease in AT1a mRNA, whereas treatment with frusemide, losartan or ramipril had no effect on the AT1a or AT1b mRNA levels. Rats fed a low-sodium diet showed a 37% increase in AT1a gene expression. Dexamethasone increased AT1a mRNA by 100% and AT1b mRNA by 300%, whereas deoxycorticosterone acetate treatment decreased AT1a mRNA levels to 30% of the control values. CONCLUSIONS:The present results suggest that the expression of the predominant cardiac AT1a 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.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Della Bruna R,Ries S,Himmelstoss C,Kurtz A

subject

Has Abstract

pub_date

1995-07-01 00:00:00

pages

763-9

issue

7

eissn

0263-6352

issn

1473-5598

journal_volume

13

pub_type

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