title: Angiotensin II-dependent down-regulation of vascular natriuretic peptide type C receptor gene expression in hypertensive rats.
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 be 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.
authors.affiliation: Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: M
authors.initials: M
authors.lastname: Naruse
authors.forename: K
authors.initials: K
authors.lastname: Naruse
authors.forename: K
authors.initials: K
authors.lastname: Shionoya
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: A
authors.initials: A
authors.lastname: Tanabe
authors.forename: H
authors.initials: H
authors.lastname: Hagiwara
authors.forename: S
authors.initials: S
authors.lastname: Hirose
authors.forename: T
authors.initials: T
authors.lastname: Muraki
authors.forename: H
authors.initials: H
authors.lastname: Demura
mesh_terms: D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology; D015536:Down-Regulation; D006162:Guanylate Cyclase / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D020098:Natriuretic Peptide, C-Type; D009578:Nitrobenzenes; D010879:Piperazines; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D013777:Tetrazoles
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; D011506:Proteins; D012333:RNA, Messenger; D013777:Tetrazoles; D000804:Angiotensin II; D020098:Natriuretic Peptide, C-Type; C054218:manidipine; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C; C077793:candesartan cilexetil