Angiotensin II induces transcription and expression of alpha 1-adrenergic receptors in vascular smooth muscle cells.
Angiotensin II (ANG II) induces vascular smooth muscle contraction and functions as a growth factor stimulating vascular smooth muscle cell (VSMC) hypertrophy. We wondered whether ANG II might induce expression of alpha 1-adrenergic receptors (ARs) in cultured VSMCs, which would then potentially accentuate the effects of catecholamines in the cells. Rat VSMCs were preincubated with phenoxybenzamine to inactivate alpha 1-ARs; the cells were then treated with ANG II for 24 h. ANG II-treated cells expressed an increased number of alpha 1-ARs compared with controls, suggesting that ANG II increased the rate of alpha 1-AR synthesis. ANG II markedly induced accumulation of alpha 1A/D- and alpha 1B-AR mRNAs in a concentration- and time-dependent manner. This effect of ANG II was blocked by the specific ANG II-receptor agonist [Sar1-Ile8]ANG II. ANG II-induced accumulation of alpha 1A/D-AR mRNAs was completely abolished by transcriptional inhibitor actinomycin D. ANG II markedly increased the transcriptional rate of the alpha 1A/D-AR gene without changing stability of alpha 1A/D-AR mRNAs. Protein kinase C (PKC) activator 4 beta-phorbol 12-myristate 13-acetate also induced accumulation of alpha 1A/D-AR mRNAs, and PKC inhibitor H-7 completely blocked ANG II-induced accumulation of the alpha 1A/D-AR mRNAs. Neither the biologically inactive ANG II analogue des-Phe8-ANG II nor the calcium ionophores A-23187 and BAY K-8466 induced alpha 1A/D-AR mRNAs. Finally, ANG II preincubation increased alpha 1-AR agonist phenylephrine-stimulated expression of the c-fos gene.(ABSTRACT TRUNCATED AT 250 WORDS)
Hu
Z W
ZW
Department of Medicine, Stanford University School of Medicine, Palo Alto, California.
Shi
X Y
XY
Okazaki
M
M
Hoffman
B B
BB
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000494:pharmacology; D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
D017931:DNA Primers; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D010643:Phenoxybenzamine; D000804:Angiotensin II; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D011493:Protein Kinase C