T. Yoshimoto et al., ANGIOTENSIN II-DEPENDENT DOWN-REGULATION OF VASCULAR NATRIURETIC PEPTIDE TYPE-C RECEPTOR GENE-EXPRESSION IN HYPERTENSIVE RATS, Endocrinology, 137(3), 1996, pp. 1102-1107
Biological actions of natriuretic peptide (NP) are determined by the c
ondition of the receptor as well as that of the the hormone. Although
we previously demonstrated in hypertensive rats the up-regulation of N
P-A receptor that mediates various biological actions of NPs, the path
ophysiologic significance of NP-C receptor, another subtype thought to
be related to clearance of NPs and possibly to biological actions, re
mains unknown. In the present study, we determined NP-C receptor messe
nger RNA (mRNA) level in the aortic tissue of stroke-prone spontaneous
ly 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, r
eversed the down-regulated NP-C receptor mRNA in SHR-SP/Izm to the lev
el in WKY/Izm, whereas the latter was more potent in decreasing the bl
ood pressure. In cultured aortic smooth muscle cells, the NP-C recepto
r 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 leve
l was altered by Ang II. These findings indicate that vascular NP-C re
ceptor 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.