Angiotensin II-dependent down-regulation of vascular natriuretic peptide type C receptor gene expression in hypertensive rats

Takanobu Yoshimoto, Mitsuhide Naruse, Kiyoko Naruse, Kiseko Shionoya, Masami Tanaka, Akiyo Tanabe, Hiromi Hagiwara, Shigehisa Hirose, Takamura Muraki, Hiroshi Demura

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Biological actions of natriuretic peptide (NP) are determined by the condition of the receptor as well as that of the hormone. Although we previously demonstrated in hypertensive rats the up-regulation of NP-A receptor that mediates various biological actions of NPs, the pathophysiologic significance of NP-C receptor, another subtype thought to he related to clearance of NPs and possibly to biological actions, remains unknown. In the present study, we determined NP-C receptor messenger RNA (mRNA) level in the aortic tissue of stroke prone spontaneously hypertensive rats (SHR-SP/Izm) and in cultured aortic smooth muscle cells by ribonuclease protection assay. The aortic NP-C receptor mRNA level in SHR-SP/Izm was significantly lower than that in the control WKY/Izm. Oral administration of an angiotensin (Ang) II receptor (AT1) antagonist, TCV-116, but not a calcium channel blocker, manidipine, reversed the down-regulated NP-C receptor mRNA in SHR-SP/Izm to the level in WKY/Izm, whereas the latter was more potent in decreasing the blood pressure. In cultured aortic smooth muscle cells, the NP-C receptor was the predominant subtype. Ang II decreased the NP-C receptor mRNA level in a dose-dependent manner, but this effect was reversed by an AT1 antagonist, CV-11974. Neither the NP-A nor NP-B receptor mRNA level was altered by Ang II. These findings indicate that vascular NP-C receptor is down-regulated via Ang II-mediated mechanism in SHR-SP/Izm. The phenomenon, together with the up-regulation of the NP-A receptor, may play an important role in counteracting hypertension by enhancing the action of NPs.

元の言語English
ページ(範囲)1102-1107
ページ数6
ジャーナルEndocrinology
137
発行部数3
DOI
出版物ステータスPublished - 1996 1 1

ASJC Scopus subject areas

  • Endocrinology

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    Yoshimoto, T., Naruse, M., Naruse, K., Shionoya, K., Tanaka, M., Tanabe, A., Hagiwara, H., Hirose, S., Muraki, T., & Demura, H. (1996). Angiotensin II-dependent down-regulation of vascular natriuretic peptide type C receptor gene expression in hypertensive rats. Endocrinology, 137(3), 1102-1107. https://doi.org/10.1210/endo.137.3.8603580