R. Dellabruna et al., EXPRESSION OF CARDIAC ANGIOTENSIN-II AT(1) RECEPTOR GENES IN RAT HEARTS IS REGULATED BY STEROIDS BUT NOT BY ANGIOTENSIN-II, Journal of hypertension, 13(7), 1995, pp. 763-769
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.