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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Abstract

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.

Original languageEnglish
Pages (from-to)1102-1107
Number of pages6
JournalEndocrinology
Volume137
Issue number3
DOIs
Publication statusPublished - 1996 Jan 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