肾上腺髓质素对离体肺动脉缺氧性收缩作用机制的研究

The Effects of Adrenomedullin on Hypoxic Vasocontraction Isolated Pulmonary Artery Rings in Rabbit

目的 探讨肾上腺髓质素 (ADM)在缺氧性肺血管收缩发生中的作用及其与内源性一氧化氮 (NO)的关系。方法 取日本长耳白兔制备内皮完整的离体肺动脉环 18个 ,随机分为对照组、ADM组和ADM +Nω-硝基 -L -精氨酸 (L -NNA)组。利用离体血管环张力测定技术 ,观察去甲肾上腺素(NA)预收缩肺动脉环在急性缺氧介质中的收缩反应 ,并观察ADM和ADM +L -NNA孵育对缺氧收缩反应的影响。结果 在常氧条件下 ,经ADM孵育的肺动脉环NA预收缩反应张力较对照组降低 2 4 .9% (P<0 .0 1) ,而ADM +L -NNA共同孵育的肺动脉环NA预收缩反应张力明显高于ADM组 (P <0 .0 1) ,但与对照组比较无显著差异 (P >0 .0 5 ) ;NA预收缩的肺动脉环在急性缺氧介质中立即出现明显的缺氧收缩峰 ,而经ADM孵育的肺动脉环NA预收缩后缺氧收缩峰的幅度较单纯NA预收缩的肺动脉环降低了 36 .4 % (P <0 .0 5 ) ;而ADM +L -NNA共同孵育肺动脉环NA预收缩后的缺氧收缩张力与对照组比较差异无显著性意义 (P >0 .0 5 )。结论 ADM可抑制缺氧性肺动脉收缩 ,其作用可能是由NO介导的。

Objective To investigate the effects of adrenomedullin(ADM) on rabbit pulmonary artery (PA) rings with endothelium and preconstricted by noradrenaline (NA) under normoxic and hypoxic conditions and the relationship between ADM and nitric oxide(NO). Methods 18 isolated pulmonary artery rings with endothelium from adult Japan white rabbits were prepared and randomly divided into 3 groups (n=6):①control gruop,②ADM incubation group, ③ADM+N ω-nitro-L-arginine(L-NNA)incubation group. With isolated arterial rings technique, it was observed that ADM and ADM+L-NNA act on vascular smooth muscle tone of pulmonary artery ring preconstricted by NA. Results Under normoxic condition, ADM incubation reduced 24.9% contractile response to α-adrenoceptor agonist NA on the pulmonary arterial rings compared with control and the action of ADM was abolished in ADM+L-NNA incubation group. Under hypoxic condition, pulmonary arterial rings preconstricted by NA happened acute hypoxic vasocontraction responses. ADM incubation reduced 36.4% the acute hypoxic vasocontraction response of the pulmonary arterial rings preconstricted by NA compared with hypoxic control (P<0.05) and the actions that ADM decreased acute hypoxic vasocontraction response on the pulmonary arterial rings preconstricted by NA were similarly reversed by incubating combined with L-NNA. Conclusion These results suggest that ADM be a potent vasodilator of the pulmonary artery in vitro under normoxic and hypoxic conditions, and that the ADM-induced relaxation of the pulmonary artery rings preconstricted by NA under hypoxic conditions be impaired by L-NNA.The vasorelaxant actions of ADM are partially mediated by NO.