Pulmonary Hypertension Group, Center for Perinatal Research, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Am J Physiol Heart Circ Physiol. 2013 Jan 15;304(2):H195-205. doi: 10.1152/ajpheart.00188.2012. Epub 2012 Oct 26.
Chronic hypoxia (CH)-induced pulmonary hypertension is characterized by vasoconstriction and vascular remodeling, leading to right ventricular dysfunction. Given the role of arterial compliance (C(a)) in right ventricular work, a decrease in C(a) would add to right ventricular work. Nitric oxide (NO) is a potent vasodilator made by NO synthases from L-arginine (L-Arg). However, little is known of the effect of L-Arg on vascular compliance (C(v)) in the lung. We hypothesized that exposure to CH would decrease C(a) and that this effect would be reversed by exogenous L-Arg. Sprague-Dawley rats were exposed to either normoxia or CH for 14 days; the lungs were then isolated and perfused. Vascular occlusions were performed and modeled using a three-compliance, two-resistor model. Pressure-flow curves were generated, and a distensible vessel model was used to estimate distensibility and a vascular resistance parameter (R(0)). Hypoxia resulted in the expected increase in arterial resistance (R(a)) as well as a decrease in both C(a) and C(v). L-Arg had little effect on R(a), C(a), or C(v) in isolated lungs from normoxic animals. L-Arg decreased R(a) in lungs from CH rats and redistributed compliance to approximately that found in normoxic lungs. CH increased R(0), and L-Arg reversed this increase in R(0). L-Arg increased exhaled NO, and inhibition of L-Arg uptake attenuated the L-Arg-induced increase in exhaled NO. These data demonstrate that the CH-induced decrease in C(a) was reversed by L-Arg, suggesting that L-Arg may improve CH-induced right ventricular dysfunction.
慢性缺氧（CH）诱导的肺动脉高压的特征是血管收缩和血管重塑，导致右心室功能障碍。鉴于动脉顺应性（C(a)）在右心室工作中的作用，C(a)的降低会增加右心室的工作量。一氧化氮（NO）是一种由 L-精氨酸（L-Arg）产生的强效血管扩张剂。然而，对于 L-Arg 对肺部血管顺应性（C(v)）的影响知之甚少。我们假设 CH 暴露会降低 C(a)，并且这种作用可以被外源性 L-Arg 逆转。将 Sprague-Dawley 大鼠暴露于常氧或 CH 中 14 天；然后将肺部分离并灌注。进行血管闭塞并使用三顺应性、两电阻器模型进行建模。生成压力-流量曲线，并使用可扩张血管模型估计可扩张性和血管阻力参数（R(0)）。缺氧导致预期的动脉阻力（R(a)）增加，以及 C(a)和 C(v)的降低。L-Arg 对常氧动物离体肺中的 R(a)、C(a)或 C(v)几乎没有影响。L-Arg 降低了 CH 大鼠肺中的 R(a)，并将顺应性重新分配至接近常氧肺的水平。CH 增加了 R(0)，而 L-Arg 逆转了这种 R(0)的增加。L-Arg 增加了呼出的 NO，并且抑制 L-Arg 摄取减弱了 L-Arg 诱导的呼出的 NO 的增加。这些数据表明，L-Arg 逆转了 CH 诱导的 C(a)降低，这表明 L-Arg 可能改善 CH 诱导的右心室功能障碍。
