Down-regulation of C-type natriuretic peptide receptor by vasonatrin peptide in cardiac myocytes and fibroblasts.
OBJECTIVE
To investigate the regulatory effects of vasonatrin peptide (VNP) on the expression of C-type natriuretic peptide receptor (NPR-C) in cultured neonatal rat cardiac myocytes and fibroblasts.


METHODS
Quantitative RT-PCR was undertaken to evaluate the levels of NPR-C mRNA and radioimmunoassay was used to determine the formation of intracellular cGMP.


RESULTS
Twenty-four hours hypoxic exposure increased the level of NPR-C mRNA in cardiomyocytes, while did not alter the expression of NPR-C in cardiac fibroblasts. VNP (10(-8)-10(-6) mol/L) reduced the levels of NPR-C mRNA in cardiac myocytes induced by hypoxia in a concentration-dependent manner, and with high concentration (10(-6) mol/L) also decreased the expression of NPR-C in cardiac fibroblasts and air-control cardiac myocytes. The inhibitory effects of VNP on the expression of NPR-C was mimicked by 8-bromo-cGMP 10(-6) mol/L (a membrane permeable analog of cGMP). VNP (10(-8)-10(-6) mol/L) increased the formation of intracellular guanosine-3',5'-cyclic monophosphate (cGMP) in both cardiac myocytes and fibroblasts. HS-142-1, the particulate guanylyl cyclase-coupled receptor antagonist, partially abrogated the above effects of VNP.


CONCLUSIONS
Hypoxic exposure for 24 h up-regulated the expression of NPR-C in cultured neonatal rat cardiac myocytes. VNP decreased the expression of NPR-C in cardiac myocytes and fibroblasts under both air-control and hypoxic condition, which was at least partially mediated by guanylate cyclase linked natriuretic peptide receptors through increasing the intracellular cGMP.
Lü
Shun-yan
SY
Department of Physiology, Fourth Military Medical University, Xi-an 710032, China.
Zhu
Miao-zhang
MZ
Wang
Dian-shi
DS
Yu
Jun
J
Guo
Hai-tao
HT
Hu
Yu-zhen
YZ
Wei
Qi-ming
QM
D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000096:biosynthesis* / Q000235:genetics; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; C068986:ventricular natriuretic peptide, eel; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C; D006152:Cyclic GMP