间尼索地平对低氧性肺动脉高压大鼠的作用

Effects of m-nisoldipine on hypoxic pulmonary hypertension in rats

目的探讨间尼索地平(m-nisoldipine,M-NIS)对低氧性肺动脉高压(hypoxic pulmonary hypertension,HPH)大鼠肺动脉压和肺动脉重构的作用。方法 (1)将50只Wistar大鼠随机分为正常对照组、模型组、M-NIS组,硝苯地平(nifedipine,NIF)组,模型组20只,其他组各10只。正常对照组在自然环境下饲养4周。剩余3组均置于低压低氧舱中饲养4周,8h/d。自第2周起,各组每天进舱前给药1次,连续给药3周。4周后,比较各组大鼠的平均肺动脉压(mean pulmonary arterial pressure,mPAP)、右心室收缩压(right ventricular systolic pressure,RVSP)、右心室肥厚指数(right ventricular hypertrophy index,RVHI),计算出管壁厚度占外径的百分比(WT%)和管壁面积占血管总面积的百分比(WA%)。(2)取模型组大鼠的肺动脉干制备血管环,用离体血管实验法,以KCl、去氧肾上腺素(phenylephrine,PHE)在含钙离子和不含钙离子的K-H液中预收缩离体大鼠肺动脉环,观察M-NIS对血管收缩的影响。结果 (1)M-NIS和NIF组大鼠的mPAP、RVSP、RVHI、WT%、WA%显著低于模型组(P<0.05),模型组大鼠的上述指标显著高于正常对照组(P<0.05)。(2)在含钙离子的K-H液中,M-NIS抑制KCl(30mmol/L、50mmol/L)和PHE(5×10^(-8) mol/L、5×10^(-7) mol/L)所致血管收缩的IC50分别为8.52×10^(-9) mol/L、1.29×10^(-7) mol/L和2.81×10^(-8) mol/L、5.23×10^(-7) mol/L。在无钙离子K-H液中,间尼索地平无抑制离体血管收缩的作用。结论间尼索地平对大鼠的HPH有治疗作用。

Objective To discover the effects of m-nisoldipine(M-NIS)on pulmonary arterial pressure and pulmonary vascular remodeling in hypoxic pulmonary hypertension(HPH)rats.Methods(1)Fifty wistar rats were randomly divided into four groups:normal group,model group,M-NIS group and nifedipine(NIF)group.There were twenty rats in the model group and ten rats in other groups respectively.Rats in the normal group were kept in a normal environment for four weeks.Rats in other groups were kept in a hypobaric oxygen chamber for eight hours each day for four weeks.Rats in each group were administrated with corresponding drugs from the second week for three weeks.At the end of the fourth weeks,the mPAP,RVSP,RVHI,WT% and WA% in each group were measured or calculated.(2)The isolated rat pulmonary arterial rings were selected from the model group.We used isolated artery experiment to observe the antagonistic effects of M-NIS on the contraction induced by KCl and PHE in isolated rat pulmonary arterial rings in the calciferous and calcium-free K-H solution.Results(1) The mPAP,RVSP,RVHI,WT%,WA%in M-NIS and NIF groups were lower than those of the model group(P<0.05),and the above indexes in model group were higher than those of the normal group(P<0.05).(2)In the calciferous K-H solution,M-NIS has antagonistic effect on the contraction induced by KCl(30 mmol/L,50 mmol/L)and PHE(5×10^(-8) mol/L,5×10^(-7) mol/L)in isolated rat pulmonary arterial rings.The IC50 was 8.52×10^(-9) mol/L,1.29×10^(-7) mol/L and2.81×10^(-8) mol/L,5.23×10^(-7) mol/L,respectively.In the calcium-free K-H solution,M-NIS had no effect.Conclusion M-NIS has therapeutical effect in hypoxic pulmonary hypertension rats.