慢性缺氧对大鼠肺动脉内皮依赖性舒张反应及cGMP含量的影响

EFFECT OF CHRONIC HYPOXIA ON ENDOTHELIUM-DEPENDENT RELAXATION AND THE CONTENT OF cCMP IN RAT PULMONARY ARTERY

本实验观察了慢性缺氧对大鼠肺动脉内皮依赖性舒张反应和肺动脉内环磷酸鸟苷(cGMP)含量的影响。乙酰胆碱(ACh)和三磷酸腺苷(ATP)可使正常大鼠的离体肺动脉产生内皮依赖性舒张反应,其舒张作用不受消炎痛的影响,但被甲烯蓝完全抑制。慢性缺氧明显减低了 ACh 和 ATP 诱发的大鼠肺内和肺外动脉的内皮依赖性舒张反应。当 ACh 浓度为10^(-6)mol/L 时,缺氧组大鼠肺内和肺外动脉舒张百分数分别为对照组的61.3%和59.2%;当 ATP浓度为1.8×10^(-5)mol/L 时,缺氧组大鼠肺内和肺外动脉舒张反应分別为对照组的64.9%和55.3%。慢性缺氧也减低了硝普钠(SNP)诱发的大鼠肺动脉非内皮依赖性舒张反应。慢性缺氧显著减低了大鼠肺动脉内 cGMP 的含量。缺氧组和对照组大鼠肺动脉内 cGMP 的基础含量分别是51.9±5.7 pmol/g wet wt.(n=14)和84.9±9.7 pmol/g wet wt.(n=14),p<0.01;经 10^(-7)mol/L ACh 刺激后分别是91.4±7.3 pmol/g wet wt.(n=5)和240.8±30.6pmol/g wet wt.(n=5),p<0.01。慢性缺氧可能抑制了肺动脉平滑肌细胞胞浆中可溶性鸟苷酸环化酶,从而减低了肺动脉对内皮舒张因子和 SNP 的舒张反应性。

This experiment was designed to investigate whether chronic hypoxia affectrat pulmonary artery(PA)endothelium-dependent relaxation and the content ofcGMP in PA.Both ACh and ATP could induce endothelium-dependent relaxationof PA,not prevented by indomethacin,but completely abolished by methyleneblue.These results indicated that vasodilatation of PA induced by both ACh andATP is mediated by EDRF(endothelium-derived relaxing factor).Chronichypoxia significantly depressed PA endothelium-dependent relaxation.The percentrelaxation of IPPA and EPPA by 10^(-6)mol/L ACh was 61.3% and 59.2% of thosein control,and the percent relaxation of IPPA and EPPA by 1.8×10^(-5)mol/LATP was 64.9% and 55.3% respectively of the control.Chronic hypoxia also de-pressed SNP-induced endothelium-independent relaxation.Chronic hypoxia sig-nificantly decreased the content of cGMP in PA.The basic level of cGMP was51.9±5.7(n=14) in hypoxia group and 84.9±9.7(n=14)pmol/g wet wt.incontrol group(P<0.01).After treatment of PA with ACh(10^(-7)mol/L),thecontent of cGMP was 91.4±7.3(n=5) pmol/g wet wt.in hypoxic group and240.8±30.6(n=5)pmol/g wet wt.in control group(P<0.01).Our datasuggest that chronic hypoxia might depress rat pulmonary artery endothelium-dependent relaxation through the inhibition of soluble gnanylate cyclase in vascularsmooth muscle cells.