Fineman J R, Crowley M R, Heymann M A, Soifer S J
Department of Pediatrics, University of California, San Francisco 94143.
J Appl Physiol (1985). 1991 Aug;71(2):735-41. doi: 10.1152/jappl.1991.71.2.735.
In vitro evidence suggests that resting pulmonary vascular tone and endothelium-dependent pulmonary vasodilation are mediated by changes in vascular smooth muscle concentrations of guanosine 3',5'-cyclic monophosphate (cGMP). We investigated this hypothesis in vivo in 19 mechanically ventilated intact lambs by determining the hemodynamic effects of methylene blue (a guanylate cyclase inhibitor) and then by comparing the hemodynamic response to five vasodilators during pulmonary hypertension induced by the infusion of U-46619 (a thromboxane A2 mimic) or methylene blue. Methylene blue caused a significant time-dependent increase in pulmonary arterial pressure. During U-46619 infusions, acetylcholine, ATP-MgCl2, sodium nitroprusside, isoproterenol, and 8-bromo-cGMP decreased pulmonary arterial pressure. During methylene blue infusions, the decreases in pulmonary arterial pressure caused by acetylcholine and ATP-MgCl2 (endothelium-dependent vasodilators) and sodium nitroprusside (an endothelium-independent guanylate cyclase-dependent vasodilator) were attenuated by greater than 50%. The decreases in pulmonary arterial pressure caused by isoproterenol and 8-bromo-cGMP (endothelium-independent vasodilators) were unchanged. This study in intact lambs supports the in vitro evidence that changes in vascular smooth muscle cell concentrations of cGMP in part mediate resting pulmonary vascular tone and endothelium-dependent pulmonary vasodilation.
体外实验证据表明，静息状态下的肺血管张力和内皮依赖性肺血管舒张是由血管平滑肌中鸟苷 3',5'-环磷酸（cGMP）浓度的变化介导的。我们在 19 只机械通气的完整羔羊体内对这一假设进行了研究，方法是先测定亚甲蓝（一种鸟苷酸环化酶抑制剂）的血流动力学效应，然后比较在输注 U-46619（一种血栓素 A2 类似物）或亚甲蓝诱导的肺动脉高压期间对五种血管扩张剂的血流动力学反应。亚甲蓝导致肺动脉压出现显著的时间依赖性升高。在输注 U-46619 期间，乙酰胆碱、ATP-MgCl2、硝普钠、异丙肾上腺素和 8-溴-cGMP 可降低肺动脉压。在输注亚甲蓝期间，乙酰胆碱和 ATP-MgCl2（内皮依赖性血管扩张剂）以及硝普钠（一种不依赖内皮的鸟苷酸环化酶依赖性血管扩张剂）引起的肺动脉压下降减弱了 50%以上。异丙肾上腺素和 8-溴-cGMP（不依赖内皮的血管扩张剂）引起的肺动脉压下降则没有变化。这项在完整羔羊身上进行的研究支持了体外实验证据，即血管平滑肌细胞中 cGMP 浓度的变化部分介导了静息状态下的肺血管张力和内皮依赖性肺血管舒张。
