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目的：研究血管钠肽（ＶＮＰ）对慢性低氧性肺动脉高压（ＨＰＨ）大鼠的治疗作用和肺动脉平滑肌细胞（ＰＡＳＭＣ）增殖的影响，并与Ｃ型钠尿肽（ＣＮＰ）和心房钠尿肽（ＡＮＰ）作比较。方法：采用整体静脉给药、离 体血管灌流和ＰＡＳＭＣ培养等方法，测定肺血流动力学参数、离体肺动脉的等长张力和ＰＡＳＭＣ增殖的变化。 结果：（１）ＶＮＰ、ＣＮＰ和ＡＮＰ都能有效降低ＨＰＨ大鼠的平均肺动脉压（ｍＰＡＰ），Ｐ＜０．０５～０．０１；除ＣＮＰ外， ＶＮＰ和ＡＮＰ并能明显降低肺血管阻力（ＰＶＲ），Ｐ＜０．０５～０．０１，其中ＶＮＰ降低ｍＰＡＰ和ＰＶＲ的作用明显 大于ＣＮＰ和ＡＮＰ。（２）ＶＮＰ对离体肺动脉呈浓度依赖性舒张作用，该作用不受内皮细胞的影响；但在浴槽内 预先加入格列苯脲或普萘洛尔可显著降低肺动脉对ＶＮＰ和ＣＮＰ的最大舒张反应（Ｒｍａｘ），Ｐ＜０．０５～０．０１，而 对ＡＮＰ却无明显影响。（３）ＶＮＰ能明显抑制低氧介导的ＰＡＳＭＣ的增殖及ＤＮＡ合成，其作用明显大于ＣＮＰ 和ＡＮＰ。结论：ＶＮＰ对ＨＰＨ具有显著的治疗作用，它是一个新型、强效、非内皮依赖性的血管松弛多肽和细 胞增殖负调控因子。
OBJECTIVE: To study the effects of vascular sodium peptide (VNP) on the treatment of chronic hypoxic pulmonary hypertension (HPH) rats and the proliferation of pulmonary artery smooth muscle cells (PASMC), and to study the effects of VNP and atrial natriuretic peptide (ANP) for comparison. Methods: The parameters of pulmonary hemodynamics, isometric tension of isolated pulmonary artery and the proliferation of PASMC were measured by the methods of total intravenous administration, ex vivo vascular perfusion and PASMC culture. Results: (1) Both VNP, CNP and ANP could effectively reduce the mean pulmonary arterial pressure (mPAP) in HPH rats, P <0.05 ~ 0.01. In addition to CNP, VNP and ANP significantly reduced pulmonary vascular resistance PVR), P <0.05 ~ 0.01. The effect of VNP in reducing mPAP and PVR was significantly greater than CNP and ANP. (2) The effect of VNP on pulmonary vasoconstriction in a concentration-dependent manner was not affected by endothelial cells. However, pretreatment with glibenclamide or propranolol in the bath significantly reduced the maximal relaxation of pulmonary artery to VNP and CNP Reaction (Rmax), P <0.05 ~ 0.01, but no significant effect on ANP. (3) VNP can significantly inhibit hypoxia-mediated PASMC proliferation and DNA synthesis, its role was significantly greater than the CNP and ANP. Conclusion: VNP has a significant therapeutic effect on HPH. It is a novel, potent, non-endothelium dependent vascular relaxant peptide and a negative regulator of cell proliferation.