Sprague R S, Stephenson A H, Dimmitt R A, Weintraub N L, Branch C A, McMurdo L, Lonigro A J
Department of Medicine, Saint Louis University School of Medicine, MO 63104, USA.
Pol J Pharmacol. 1994 Nov-Dec;46(6):579-85.
Endogenous nitric oxide (NO) opposes the vasoconstriction that occurs when lungs are ventilated with a hypoxic gas mixture. However, the contribution of NO to pulmonary vascular resistance when alveolar gas tension is not reduced remains to be defined. Here, we investigated the hypothesis that endogenous NO is a determinant of pulmonary vascular resistance in isolated perfused rabbit lungs ventilated with a normoxic gas mixture. Moreover, we wished to establish that, as flow rate increases, the contribution of NO to vascular resistance increases. In addition, we examined the contribution of NO to the longitudinal distribution of pulmonary vascular resistance. Pressure-flow curves were generated in isolated blood perfused rabbit lungs by varying flow rate from 50 ml/min to 300 ml/min in the presence and absence of the cyclooxygenase inhibitor, indomethacin (100 microM) and the inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). Indomethacin did not alter total pulmonary vascular resistance or the longitudinal distribution of resistance. In contrast, L-NAME administration resulted in significant, flow-related increases in total vascular resistance, i.e., after L-NAME, as flow rate increased, the increment in resistance increased. L-NAME-induced increases in total pulmonary vascular resistance were the result of flow-related increases in the arterial component of vascular resistance. These results provide support for the hypothesis that NO is an important determinant of pulmonary vascular resistance in the rabbit and that the major site of NO activity resides in the arterial side of that circulation.
内源性一氧化氮（NO）可对抗肺部用低氧气体混合物通气时发生的血管收缩。然而，当肺泡气体张力未降低时，NO对肺血管阻力的作用仍有待确定。在此，我们研究了以下假设：内源性NO是在用常氧气体混合物通气的离体灌注兔肺中肺血管阻力的一个决定因素。此外，我们希望证实，随着流速增加，NO对血管阻力的作用会增强。另外，我们研究了NO对肺血管阻力纵向分布的作用。在存在和不存在环氧化酶抑制剂吲哚美辛（100微摩尔）和NO合成抑制剂NG-硝基-L-精氨酸甲酯（L-NAME，100微摩尔）的情况下，通过将流速从50毫升/分钟变化至300毫升/分钟，在离体血液灌注兔肺中生成压力-流量曲线。吲哚美辛未改变总肺血管阻力或阻力的纵向分布。相反，给予L-NAME导致总血管阻力出现与流量相关的显著增加，即给予L-NAME后，随着流速增加，阻力的增加幅度增大。L-NAME引起的总肺血管阻力增加是血管阻力动脉部分与流量相关增加的结果。这些结果支持了以下假设：NO是兔肺血管阻力的一个重要决定因素，且NO活性的主要部位位于该循环的动脉侧。
