Chronic EDRF inhibition and hypoxia: effects on pulmonary circulation and systemic blood pressure.
Chronic EDRF inhibition and hypoxia: effects on pulmonary circulation and systemic blood pressure.
复制标题
DOI：
10.1152/jappl.1993.75.4.1748
复制
发表时间：
1993-10
影响因子：
3.3
通讯作者：
V. Hampl;S. Archer;Daniel P. Nelson;E. Weir
中科院分区：
文献类型：
--
作者：
V. Hampl;S. Archer;Daniel P. Nelson;E. Weir
有研究认为，慢性缺氧性肺动脉高压是由于慢性缺氧性抑制内皮源性松弛因子(EDRF)的合成所致。我们通过研究N omega-硝基-L-精氨酸甲酯(L-NAME)慢性抑制血管内皮细胞生长因子是否会引起与慢性缺氧类似的肺动脉高压来验证这一假说。给常氧和低氧条件下的大鼠灌服L(1.85 mM)水3wk。与慢性缺氧不同，L的慢性治疗不会增加肺动脉压。慢性L治疗使心输出量减少，平均体动脉压升高。慢性低氧使离体肺的血管压力-流量关系向高压方向移动，而L的摄入量对压力-流量关系的影响较小。在离体肺中，血管紧张素II引起的血管收缩和硝普钠引起的急性缺氧和血管扩张，在常氧和慢性缺氧条件下均能增加L的作用。慢性低氧，而不是L的名字，诱导了高血压性肺血管重构。慢性补充血管内皮细胞生长因子前体L-精氨酸对慢性缺氧性肺动脉高压无明显影响。我们的结论是，在我们的模型中，L-NAME诱导的慢性内皮细胞生长因子缺乏状态并不能模拟慢性缺氧性肺动脉高压。此外，EDRF在肺的基础音调调节中的重要性低于在体循环中的重要性。
It has been suggested that chronic hypoxic pulmonary hypertension results from chronic hypoxic inhibition of endothelium-derived relaxing factor (EDRF) synthesis. We tested this hypothesis by studying whether chronic EDRF inhibition by N omega-nitro-L-arginine methyl ester (L-NAME) would induce pulmonary hypertension similar to that found in chronic hypoxia. L-NAME (1.85 mM) was given for 3 wk in drinking water to rats living in normoxia or hypoxia. Unlike chronic hypoxia, chronic L-NAME treatment did not increase pulmonary arterial pressure. Cardiac output was reduced and mean systemic arterial pressure was increased by chronic L-NAME treatment. The vascular pressure-flow relationship in isolated lungs was shifted toward higher pressures by chronic hypoxia and, to a lesser degree, by L-NAME intake. In isolated lungs, vasoconstriction in response to angiotensin II and acute hypoxia and vasodilation in response to sodium nitroprusside were increased by chronic L-NAME treatment in normoxia and chronic hypoxia. Chronic hypoxia, but not L-NAME, induced hypertensive pulmonary vascular remodeling. Chronic supplementation with the EDRF precursor L-arginine did not have any significant effect on chronic hypoxic pulmonary hypertension. We conclude that the chronic EDRF deficiency state, induced by L-NAME, does not mimic chronic hypoxic pulmonary hypertension in our model. In addition, EDRF proved to be less important for basal tone regulation in the pulmonary than in the systemic circulation.