Effect of AT2 receptor on expression of AT1 and TGF-beta receptors in VSMCs from SHR.
We recently reported that overexpression of the angiotensin II type 2 (AT2) receptor downregulates the AT1a receptor through the bradykinin/NO pathway in a ligand-independent manner in vascular smooth muscle cells (VSMCs). In the present study, we investigated the effect of AT2 receptor overexpression on the expression of the AT1a receptor and transforming growth factor-beta (TGF-beta) receptor subtypes in VSMCs from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Transfection of the AT2 receptor gene downregulated expression of the AT1a receptor in VSMCs from WKY, but did not affect expression of the AT1a receptor in VSMCs from SHR. Transfection of the AT2 receptor abolished DNA synthesis in response to angiotensin II in VSMCs from WKY; in VSMCs from SHR, basal DNA synthesis was suppressed, but DNA synthesis in response to Ang II was not altered. The NO substrate L-arginine augmented downregulation of the AT1a receptor in VSMCs from WKY, whereas it did not affect expression of the AT1a receptor in VSMCs from SHR. In response to AT2 receptor transfection, expression of TGF-beta type I receptor mRNA was suppressed significantly in VSMCs from WKY, whereas expression of TGF-beta type I receptor was not altered in VSMCs from SHR. These results suggest that the AT2 receptor downregulates AT1a and TGF-beta type I receptors in normal VSMCs, but not in SHR-derived VSMCs. The lack of downregulation of the AT1a receptor may contribute, in part, to the exaggerated growth of VSMCs from SHR.
Su
Jin-Zi
JZ
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Fukuda
Noboru
N
Jin
Xue-Qing
XQ
Lai
Yi-Mu
YM
Suzuki
Ryo
R
Tahira
Yoshiko
Y
Takagi
Hiroto
H
Ikeda
Yukihiro
Y
Kanmatsuse
Katsuo
K
Miyazaki
Hitoshi
H
D030201:Activin Receptors, Type I / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D015536:Down-Regulation / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011945:Receptors, Angiotensin / Q000096:biosynthesis* / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D018125:Receptors, Transforming Growth Factor beta; D004247:DNA; D001120:Arginine; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat