[Study on the effect of endothelin and nitric oxide on DNA synthesis of pulmonary artery smooth muscle cells and modulation of hypoxia].
Increasing vasoconstriction and vascular remodeling of pulmonary vasculature are main characteristics of hypoxic pulmonary hypertension (HPH). Basal pulmonary circulatory tone is maintained by a dynamic balance of vasoconstrictors and vasodilators acting on the pulmonary vascular smooth muscle cells. Endothelin-1 (ET-1) and nitric oxide (NO) are the most important endothelium-derived vasoconstrictor (EDCF) and vasodilator (EDRF). In this report, we studied the effect of ET-1 and NO on hypoxic pulmonary vascular remodeling. We observed that ET-1 dose dependently increased DNA synthesis of pulmonary artery smooth muscle cells (PASMC), SNP, a NO generating drug, inhibited DNA synthesis of PASMC and its inhibitory effect was mediated by cGMP. Hypoxia increased the proliferative response of PASMS to ET-1 by stimulating autocrine of PASMC and decreased the inhibitory effect of SNP by reducing the activity of intra-cellular soluble guanylate cyclase. Based on the result, it is suggested that the balance of ET-1 and NO and regulation of hypoxia play important roles in hypoxic pulmonary vascular remodeling.
Feng
X
X
Institute of Basic Medical Sciences, CAMS, Beijing.
Cai
Y
Y
D000818:Animals; D002417:Cattle; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D016232:Endothelins / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D016232:Endothelins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D004247:DNA