Inhibition of hypoxia-induced proliferation and collagen synthesis by vasonatrin peptide in cultured rat pulmonary artery smooth muscle cells.
The aim of the present research is to investigate the effects of vasonatrin peptide (VNP) on hypoxia-induced proliferation and collagen synthesis in pulmonary artery smooth muscle cells (PASMCs). Smooth muscle cells isolated from rat pulmonary artery were cultured and used at passages 3-5. Cell proliferation and collagen synthesis were evaluated by cell counts, [(3)H] thymidine and [(3)H] proline incorporation. The results showed that cells exposed to hypoxia for 24 h exhibited a significant increase in [(3)H] thymidine (93%) and [(3)H] proline (52%) incorporation followed by a significant increase in cell number (47%) at 48 h in comparison with the respective normoxic controls. VNP reduced hypoxia-stimulated increase in cell proliferation in a concentration-dependent manner from 10(-8) to 10(-6) mol/L and attenuated hypoxia-induced collagen synthesis ranging from 10(-6) to 10(-5) mol/L, which is similar to but more potent than both ANP and CNP. The action of VNP on PASMCs was mimicked by 8-bromo-cGMP (10(-4) mol/L, the membrane-permeable cGMP analog), and blocked by HS-142-1 (2 x 10(-5) mol/L), the particulate guanylyl cyclase-coupled natriuretic peptide receptor antagonist, or KT-5823 (10(-6) mol/L), the cGMP-dependent protein kinase (PKG) inhibitor. The results suggest that VNP inhibits hypoxia-stimulated proliferation and collagen synthesis in cultured rat PASMCs via particulate guanylyl cyclase-coupled receptors through cGMP/PKG dependent mechanisms.
Lu
Shun-Yan
SY
Department of Physiology, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, China. lushunyan@yahoo.com
Wang
Dian-Shi
DS
Zhu
Miao-Zhang
MZ
Zhang
Qing-Hong
QH
Hu
Yu-Zhen
YZ
Pei
Jian-Ming
JM
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D015687:Cell Hypoxia; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
C068986:ventricular natriuretic peptide, eel; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D003094:Collagen; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP