Inhibition of hypoxia-induced proliferation and collagen synthesis by vasonatrin peptide in cultured rat pulmonary artery smooth muscle cells

Life Sci. 2005 May 20;77(1):28-38. doi: 10.1016/j.lfs.2004.11.026.


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.

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / pharmacology*
  • Cell Hypoxia
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Collagen / biosynthesis*
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / pharmacology
  • Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic GMP-Dependent Protein Kinases / physiology
  • Male
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Pulmonary Artery / cytology
  • Pulmonary Artery / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • ventricular natriuretic peptide, eel
  • 8-bromocyclic GMP
  • Atrial Natriuretic Factor
  • Collagen
  • Cyclic GMP-Dependent Protein Kinases
  • Cyclic GMP