Chronic hypoxia decreases arterial and venous compliance in isolated perfused rat lungs: an effect that is reversed by exogenous L-arginine.
Chronic hypoxia decreases arterial and venous compliance in isolated perfused rat lungs: an effect that is reversed by exogenous L-arginine.
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慢性缺氧会降低离体灌注大鼠肺中的动脉和静脉顺应性：外源性 L-精氨酸可逆转这种效应。
DOI：
10.1152/ajpheart.00188.2012
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Nelin,LeifD
中科院分区：
文献类型：
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作者：
Jin,Yi;Chen,Bernadette;Calvert,ThomasJ;Chicoine,LouisG;Liu,Yusen;Nelin,LeifD
慢性缺氧（CH）诱导的肺动脉高压以血管收缩和血管重构为特征，导致右心室功能障碍。考虑到动脉顺应性（Ca）在右心室作功中的作用，Ca降低会增加右心室作功。一氧化氮（NO）是一种强有力的血管扩张剂，由NO还原酶从L-精氨酸（l-Arg）产生。然而，很少有人知道的影响ofl-Arg对血管顺应性（Cv）在肺。我们假设暴露于CH会降低Ca，并且这种效应会被外源性l-Arg逆转。将Sprague-Dawley大鼠暴露于常氧或CH中14天;然后分离肺并灌注。使用三顺应性、两电阻器模型进行血管闭塞和建模。生成压力-流量曲线，并使用可扩张血管模型来估计可扩张性和血管阻力参数（R 0）。缺氧导致动脉阻力（Ra）增加，Ca 2+和Cv降低，L-Arg对离体肺的Ra、Ca 2+和Cv影响不大，L-Arg降低CH大鼠的Rain肺，并使顺应性重新分布到与常氧肺相近。CH增加R 0，l-Arg逆转R 0的增加，l-Arg增加呼出气NO，抑制l-Arg摄取可减弱l-Arg引起的呼出气NO的增加。这些数据表明，CH引起的Ca降低可被l-Arg逆转，提示l-Arg可改善CH引起的右心室功能障碍。
Chronic hypoxia (CH)-induced pulmonary hypertension is characterized by vasoconstriction and vascular remodeling, leading to right ventricular dysfunction. Given the role of arterial compliance (Ca) in right ventricular work, a decrease inCawould add to right ventricular work. Nitric oxide (NO) is a potent vasodilator made by NO synthases froml-arginine (l-Arg). However, little is known of the effect ofl-Arg on vascular compliance (Cv) in the lung. We hypothesized that exposure to CH would decreaseCaand that this effect would be reversed by exogenousl-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 (R0). Hypoxia resulted in the expected increase in arterial resistance (Ra) as well as a decrease in bothCaandCv.l-Arg had little effect onRa,Ca, orCvin isolated lungs from normoxic animals.l-Arg decreasedRain lungs from CH rats and redistributed compliance to approximately that found in normoxic lungs. CH increasedR0, andl-Arg reversed this increase inR0.l-Arg increased exhaled NO, and inhibition ofl-Arg uptake attenuated thel-Arg-induced increase in exhaled NO. These data demonstrate that the CH-induced decrease inCawas reversed byl-Arg, suggesting thatl-Arg may improve CH-induced right ventricular dysfunction.