Fineman J R, Wong J, Mikhailov T, Vanderford P A, Jerome H E, Soifer S J
Department of Pediatrics, University of California at San Francisco, 94143-0106, USA.
Pediatr Pulmonol. 1999 Mar;27(3):147-56. doi: 10.1002/(sici)1099-0496(199903)27:3<147::aid-ppul1>3.0.co;2-p.
Acute lung injury produces pulmonary hypertension, altered vascular reactivity, and endothelial injury. To determine whether acute lung injury impairs the endothelium-dependent regulation of pulmonary vascular tone, 16 lambs were studied during U46619-induced pulmonary hypertension without acute lung injury, or air embolization-induced pulmonary hypertension with acute lung injury. The hemodynamic responses to endothelium-dependent (acetylcholine, ATP, ET-1, and 4 Ala ET-1 [an ETb receptor agonist]) and endothelium-independent (nitroprusside and isoproterenol) vasodilators were compared. During U46619-induced pulmonary hypertension, all vasodilators decreased pulmonary arterial pressure and vascular resistance (P < 0.05). During air embolization-induced pulmonary hypertension, the pulmonary vasodilating effects of acetylcholine, ATP, and 4 Ala ET-1 were attenuated (P < 0.05); the pulmonary vasodilating effects of nitroprusside and isoproterenol were unchanged; and the pulmonary vasodilating effects of ET-1 were reversed, producing pulmonary vasoconstriction (P < 0.05). During air embolization, the pulmonary vasoconstricting effects of ET-1 were blocked by BQ 123, an ETa receptor antagonist. The systemic effects of the vasoactive drugs were similar during both conditions. We conclude that pulmonary hypertension with acute lung injury induced by air embolization results in endothelial dysfunction; there is selective impairment of endothelium-dependent pulmonary vasodilation and an altered response to ET-1 from pulmonary vasodilation to vasoconstriction. This altered response to ET-1 is associated with decreased ETb receptor-mediated vasodilation and increased ETa receptor-mediated vasoconstriction. Endothelial injury and dysfunction account, in part, for the altered regulation of pulmonary vascular tone during pulmonary hypertension with acute lung injury.
急性肺损伤可导致肺动脉高压、血管反应性改变及内皮损伤。为确定急性肺损伤是否会损害肺血管张力的内皮依赖性调节，对16只羔羊进行了研究，一组在U46619诱导的无急性肺损伤的肺动脉高压期间进行观察，另一组在空气栓塞诱导的伴有急性肺损伤的肺动脉高压期间进行观察。比较了对内皮依赖性（乙酰胆碱、ATP、ET-1和4 Ala ET-1 [一种ETb受体激动剂]）和内皮非依赖性（硝普钠和异丙肾上腺素）血管舒张剂的血流动力学反应。在U46619诱导的肺动脉高压期间，所有血管舒张剂均降低了肺动脉压和血管阻力（P < 0.05）。在空气栓塞诱导的肺动脉高压期间，乙酰胆碱、ATP和4 Ala ET-1的肺血管舒张作用减弱（P < 0.05）；硝普钠和异丙肾上腺素的肺血管舒张作用未改变；ET-1的肺血管舒张作用则相反，导致肺血管收缩（P < 0.05）。在空气栓塞期间，ET-1的肺血管收缩作用被ETa受体拮抗剂BQ 123阻断。两种情况下血管活性药物的全身作用相似。我们得出结论，空气栓塞诱导的伴有急性肺损伤的肺动脉高压会导致内皮功能障碍；存在内皮依赖性肺血管舒张的选择性损害以及对ET-1的反应从肺血管舒张转变为血管收缩。对ET-1的这种反应改变与ETb受体介导的血管舒张减少和ETa受体介导的血管收缩增加有关。内皮损伤和功能障碍部分解释了伴有急性肺损伤的肺动脉高压期间肺血管张力调节的改变。
