Positive feedback regulation of angiotensin II-AT1B receptor gene expression in rat adrenal glands.
This study aimed to investigate the role of endogenous angiotensin II (ANGII) in the upregulation of ANG-II AT1 receptors in adrenal glands during a low-salt intake. To this end male Sprague-Dawley rats were fed a low-salt diet (0.2 mg/g) for 10 days and were treated with the ANGII-AT1 receptor antagonist losartan (40 mg/kg per day) for 2 days, and adrenal mRNA levels for ANGII AT1A and AT1B receptors were determined by RNase protection. The low-salt diet increased AT1A and AT1B receptor mRNA levels by 90% and 220%, respectively. Losartan treatment did not change the basal AT1A mRNA level, but decreased AT1B mRNA by 50%. Treatment of rats on a low-salt diet with losartan did not change the increase of AT1A mRNA but significantly attenuated the increase of AT1B mRNA to 90% of the control value. Stimulation of endogenous ANGII levels by unilateral renal artery clipping for 2 days lowered AT1A mRNA by 25% and increased AT1B mRNA by 30%. Additional treatment with losartan did not affect the decreased AT1A mRNA levels in rats with a unilateral renal artery clip, but significantly attenuated the increase of AT1B mRNA. These findings suggest that sodium deficiency stimulates adrenal AT1A and AT1B receptor mRNA levels primarily via an ANGII-AT1-independent mechanism. The preferential increase of adrenal AT1B mRNA during a low-salt intake could be explained by the elevation of endogenous ANGII levels during sodium deficiency, suggesting that endogenous ANGII acts as an enhancer for adrenal AT1B but not for AT1A receptor gene expression via ANGII-AT1 receptors.
Wagner
C
C
Physiologisches Institut der Universität Regensburg, D-93040 Regensburg, Germany.
Kurtz
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A
D000311:Adrenal Glands / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D004039:Diet, Sodium-Restricted; D005246:Feedback; D005786:Gene Expression Regulation; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000096:biosynthesis* / Q000235:genetics; D012260:Ribonucleases / Q000378:metabolism; D015854:Up-Regulation
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D012260:Ribonucleases