PKC、Rho激酶在卡托普利舒张大鼠离体胸主动脉环中的作用

Role of PKC and Rho kinase in isolated rat thoracic aortic rings with captopril

目的研究卡托普利对大鼠胸主动脉的作用,并探讨PKC、ROCK是否参与其作用。方法离体血管环灌流装置观察卡托普利对大鼠离体胸主动脉环基础张力,以及PE或KCl预刺激血管后卡托普利的舒张作用,并使用不同工具药探讨其舒血管机制。结果卡托普利(1×10^(-7)～1×10^(-4) mol·L^(-1))对基础状态血管张力无影响,但对PE或KCl预收缩的血管具有浓度依赖性舒张作用,且内皮完整组舒张作用强于去内皮组(P<0.05)。一氧化氮合酶抑制剂L-NAME和环氧合酶抑制剂吲哚美辛可使其舒张作用部分被抑制(P<0.05)。且卡托普利可浓度依赖性抑制CaCl_2引起的血管收缩。PKC抑制剂十字孢碱或ROCK抑制剂法舒地尔可明显增强卡托普利舒血管作用(P<0.05),而PKC激动剂佛波醇酯或ROCK激动剂花生四烯酸可使其舒血管作用部分被抑制(P<0.05)。结论卡托普利浓度依赖性舒张大鼠胸主动脉机制可能与其促进NO释放、前列环素合成、减少细胞外钙内流、PKC-ROCK通路有关。

To investigate the effect of captopril on isolated rat aortic rings and its mechanisms and to explore whether Rho kinase(ROCK)and PKC participate in the relaxation of isolated rat aortic rings.Methods An isolated vascular ring perfusion device was used to observe the basal tension of rat thoracic aortic rings induced by captopril.Different drug agents were used to explore the mechanism of vasodilation and the diastolic effect of captopril on rat aortic rings that was induced by PE or KCl.Results Captopril(1×10-7~1×10-4 mol·L-1)had no significant effect on angiotasis of the basic state,but there was a concentration-dependent relaxation effect on blood vessels contracted by PE or KCl,and the vasodilatation of the intact endothelium group was stronger than that of the endothelium-reduced group(P<0.05).After blood vessels were incubated with the nitric oxide synthase inhibitor L-NAME and the COX inhibitor indometacin,their relaxing effect was partially inhibited(P<0.05).Captopril could inhibit vasoconstriction induced by CaCl 2 in a concentration-dependent manner.After using PKC inhibitor staurosporine and Rho kinase inhibitor fasudil,the effect of captopril on vasodilation was significantly enhanced(P<0.05),while after blood vessels were incubated in the PKC agonist PMA and the Rho kinase agonist AA,the captopril's vasodilatory effect was partially inhibited(P<0.05).Conclusions Captopril can relax the thoracic aorta of rats in a concentration-dependent manner.Its mechanism may be related to the promotion of NO release,prostacyclin synthesis,reduction of extracellular calcium influx,and PKC-Rho kinase pathway.