Expression of cardiac angiotensin II AT1 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 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.
Della Bruna
R
R
Physiologisches Institut, Universität Regensburg, Germany.
Ries
S
S
Himmelstoss
C
C
Kurtz
A
A
D000305:Adrenal Cortex Hormones / Q000502:physiology*; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000235:genetics*
D000305:Adrenal Cortex Hormones; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D003907:Dexamethasone