血管钠肽对低氧性肺动脉高压和肺动脉平滑肌细胞增殖的影响

Effects of Vasonatrin Peptide on Hypoxic Pulmonary Hypertension and Pulmonary Arterial Smooth Muscle Cell Proliferation in Rats

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 investigate the effects of vasonatrin peptide (VNP) on chronically hypoxic pulmonary hypertension (HPH) and pulmonary arterial smooth muscle cell (PASMC) proliferation in contrast to C-type natriuretic peptide (CNP) and atrial natriuretic peptide (ANP). Methods: The parameters of pulmonary hemodynamics and the tension of isolated pulmonary artery rings and PASMC proliferation were measured in vivo by intravenous injection of VNP, CNP and ANP and in vitro by vascular perfusion and PASMC culture method, respectively. Results: (1) VNP, CNP and ANP could effectively decrease mean pulmonary artery pressure (mPAP) in vivo (P<0. 05-0. 01) ;VNP and ANP could significantly lower pulmonary vascular resistance (PVR) except CNP; The effects of VNP on mPAP and PVR were larger than those of CNP and ANP. The effects of VNP, CNP and ANP on mean carotid artery pressure (mCAP) and heart rate (HR) were not significant (P>0. 05). (2) VNP, CNP and ANP evoked concentration-dependent relaxations in isolated pulmonary artery (P<0. 05-0. 01), but were not affected by endothelium. The maximal relaxant actions induced by VNP or CNP on pulmonary artery were significantly attenuated in organ chambers of pre-incubation with glibenclamide or propranolol in contrast no change to ANP. (3) VNP can significantly inhibit the proliferation and DNA synthesis of PASMC under hypotia. Conclusion: The results suggested that VNP can possess marked therapeutic effects on chronically hypoxic pulmonary hypertension in rats. VNP is a new type, more effective and endothelium-independent vasorelaxing peptide and negative regulatory factor of cell proliferation.