ET－1和NO对肺动脉平滑肌细胞DNA合成的作用及缺氧对其调制的研究

观察内皮素－１（ＥＴ－１）和一氧化氮（ＮＯ）在缺氧性肺血管结构重组中的作用，发现ＥＴ－１可促进肺动脉平滑肌细胞（ＰＡＳＭＣ）ＤＮＡ合成，其促进作用呈剂量依赖性；ＮＯ供应剂ＳＮＰ则起抑制作用，ＮＯ的抑制增殖作用主要由ｃＧＭＰ介导。在此基础上观察到缺氧可促进ＰＡＳＭＣ对ＥＴ－１的增殖反应，同时可抑制ＰＡＳＭＣ胞浆内可溶性鸟苷酸环化酶活性而降低ＰＡＳＭＣ对ＮＯ等舒血管药物的反应性。提示ＥＴ－１和ＮＯ及缺氧在缺氧性肺血管结构重组中具有重要的作用。

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-l(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 rnediated by cGMP. Hypoxia increased the proliferativeresponse 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 onthe result, it is suggested that the balance of ET-1 and NO and regulation of hypoxia playirnportant roles in hypoxic pulmonary vascular remodeling.