Regulation of ANG II receptor in hypertension: role of ANG II.
To investigate the role of angiotensin II (ANG II) in the development of hypertension induced by reduced renal mass (RRM) and the gene expression of ANG II type 1 (AT1) receptors in the remnant renal tissue, four groups of rats were given 1% NaCl in water and subjected to RRM, RRM+ ramipril, RRM+ losartan, or sham surgery (control). Tail-cuff systolic blood pressure was significantly higher in RRM rats than in the other three groups. Northern blot showed that AT1 gene expression was significantly decreased in RRM, RRM + ramipril, or RRM + losartan vs. control. There was no significant difference among the three RRM groups. Renal transforming growth factor-beta 1 (TGF-beta 1) mRNA levels were increased threefold (P < 0.05) in RRM, RRM+ ramipril, and RRM+ losartan vs. control. There was no significant difference among the three RRM groups. We conclude that the development of RRM hypertension is ANG II dependent but not mediated by AT1 gene expression. RRM downregulates AT1 mRNA and upregulates TGF-beta 1 mRNA in the remnant renal tissue, regardless of blood pressure or plasma levels of ANG II, suggesting that these gene responses are triggered by an effect of local injury.
Wang
D H
DH
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555, USA.
Yao
A
A
Zhao
H
H
DiPette
D J
DJ
D000804:Angiotensin II / Q000235:genetics / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D009392:Nephrectomy / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000235:genetics
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D019808:Losartan; D017257:Ramipril