血管钠肽对慢性低氧性肺动脉高压的治疗作用

Therapeutic effects of vasonatrin peptide on chronical hypoxic pulmonary hypertension in rats

目的 研究血管钠肽 (vasonatrin peptide,VNP)、C型钠尿肽 (C- type natriuretic peptide,CNP)和心房钠尿肽 (a-trial natriuretic peptide,ANP)对大鼠慢性低氧性肺动脉高压(hypoxic pulmonary hypertension,HPH)的治疗作用及其机理 .方法 采用整体给药和离体血管灌流方法 ,测定肺血流动力学参数和离体肺动脉的等长张力变化 .结果 VNP,CNP和 ANP都能有效降低大鼠慢性 HPH的平均肺动脉压(m PAP) ,P<0 .0 5～ P<0 .0 1;除 CNP外 ,VNP和 ANP均能明显降低肺血管阻力 (PVR) ,P<0 .0 5～ P<0 .0 1,其中 VNP降低 m PAP和 PVR的作用明显大于 CNP和 ANP;VNP,CNP和 ANP对体循环血压 (m CAP)和心率 (HR)均无明显影响 ,P>0 .0 5 .VNP,CNP和 ANP对离体肺动脉均有浓度依赖性舒张作用 ,但不受内皮细胞的影响 ;在浴槽内预先加入优降糖或心得安可显著降低肺动脉对 VNP和 CNP的最大舒张反应 (Rmax) ,P<0 .0 5～ P<0 .0 1,而对 ANP却无明显影响 .结论 VNP对大鼠慢性 HPH具有显著的治疗作用 ,它是一个新型的、强效的、非内皮依赖性的血管松弛多肽 ,较

AIM To investigate the therapeutic effects of vason atrin peptide (VNP), C-type natriuretic peptide (CNP) and atrial natriuretic peptide (ANP) on chronical hypoxic pulmonar y hypertension (HPH) in rats. METHODS Parameters of pulmonary hemodynamics and the tension of isolated pulmonary artery rings were measured in vivo by intravenous injection of VNP, CNP and ANP and in vitro by vascu lar perfusion respectively. RESULTS VNP, CNP and ANP could eff ectively decrease mean pulmonary artery pressure (mPAP) in vivo (P<0.05～P<0.01); VNP and ANP could s ignificantly lower pulmonary vascular resistance (PVR); 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 (mC AP) and heart rate (HR) were not significant (P> 0.05). VNP, CNP and ANP evoked concentratio n-dependent relaxations in the isolated pulmonary artery (P<0.05～P< 0.0 1), but were not affected by endothelium. The maximal relaxant action induced by VNP or CNP on pulmonary artery was significantly attenuated in organ chambers of pre-incubation with glibenclamide or propranolol but no mark ed action by ANP was defected. CONCLUSION VNP can possess marked therapeutic effects on chronically hypoxic pulmonary hypertension in rats , and it is a more effective and endothelium-independent vasorelaxing peptide,which may have more potential clinical applications compared with CNP or ANP.