Angiotensin II Type 2 Receptor Gene Transfer Downregulates Angiotensin II Type 1a Receptor in Vascular Smooth Muscle Cells
作者:
Xue-Qing Jin,
Noboru Fukuda,
Jin-Zi Su,
Yi-Mu Lai,
Ryo Suzuki,
Yoshiko Tahira,
Hiroto Takagi,
Yukihiro Ikeda,
Katsuo Kanmatsuse,
Hitoshi Miyazaki,
期刊:
Hypertension: Journal of The American Heart Association
(OVID Available online 2002)
卷期:
Volume 39,
issue 5
页码: 1021-1027
ISSN:0194-911X
年代: 2002
出版商: OVID
关键词: receptors, angiotensin II;angiotensin II;muscle, smooth, vascular;nitric oxide;bradykinin
数据来源: OVID
摘要:
Two distinct subtypes of angiotensin (Ang) II receptors, type 1 (AT1) and type 2 (AT2), have been identified. Vascular smooth muscle cells (VSMCs) usually express AT1receptor. To elucidate the direct effects of the AT2receptor on the AT1receptor in VSMCs, we transfected AT2receptor gene into cultured rat VSMCs. Overexpression of AT2receptor significantly decreased expression of AT1areceptor at both the mRNA and protein levels in the presence and absence of Ang II in VSMCs. Overexpression of AT2receptor increased expression of bradykinin and inducible NO in the presence and absence of Ang II in VSMCs. Bradykinin B2receptor antagonist HOE–140 and NO synthase inhibitorN&ohgr;-nitro-l-arginine methyl ester (L-NAME) inhibited the decreases in AT1areceptor expression by the overexpression of AT2receptor in VSMCs. l-Arginine augmented the decrease in AT1areceptor expression. Overexpression of AT2receptor suppressed basal DNA synthesis and proliferation of VSMCs and abolished response of DNA synthesis to Ang II in VSMCs. Our results demonstrate that overexpression of the AT2receptor downregulates AT1areceptor expression in rat VSMCs in a ligand-independent manner that is mediated by the bradykinin/NO pathway. Downregulation of AT1areceptor is a novel mechanism by which the AT2receptor regulates growth and metabolism of VSMCs.
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