Selective upregulation of arterial endothelial nitric oxide synthase in pulmonary hypertension
Selective upregulation of arterial endothelial nitric oxide synthase in pulmonary hypertension
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DOI：
10.1152/ajpheart.1997.272.2.h806
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发表时间：
1997-02-01
影响因子：
4.8
通讯作者：
Walker, BR
中科院分区：
文献类型：
--
作者：
Resta, TC;Gonzales, RJ;Walker, BR
我们以前已经证明，动脉，而不是静脉，血管舒张反应内皮源性一氧化氮（EDNO）依赖性激动剂增强肺分离大鼠慢性缺氧（CH）诱导的肺动脉高压。这些数据表明，CH与肺动脉血管内内皮型一氧化氮合酶（eNOS）活性增加有关。此外，肺动脉压升高与选择性增强的动脉对EDNO介导的激动剂的反应性的相关性表明，动脉高血压，而不是缺氧本身，是这种反应的一个促成因素。因此，我们假设1）CH选择性上调肺动脉血管系统内的eNOS，2）野百合碱（MC）诱导的肺动脉高压选择性增强肺动脉对EDNO依赖性扩张剂的扩张，并上调动脉eNOS。我们研究了对EDNO依赖性扩张剂精氨酸加压素和离子霉素在U-46619收缩的对照和MC处理的大鼠离体灌注肺中的反应。通过双闭塞技术评估微血管压力，从而计算节段性阻力。与对照组相比，MC处理大鼠的肺表现出增强的动脉扩张精氨酸加压素。然而，对离子霉素的反应在两组之间没有差异。定量免疫细胞化学被用来比较肺eNOS免疫反应性血管从控制，CH，和MC处理的大鼠。与对照组相比，CH和NIC治疗组大鼠动脉中的eNOS染色更强烈，而CH和MC治疗对静脉中的eNOS染色没有影响。我们得出结论，肺动脉高压，或改变与高血压相关的血管机械力，可能是负责增强EDNO依赖性动脉扩张和上调动脉eNOS在CH和MC处理的大鼠肺。
We have previously demonstrated that arterial, but not venous, vasodilatory responses to endothelium-derived nitric oxide (EDNO)-dependent agonists are enhanced in lungs isolated from rats with chronic hypoxia (CH)-induced pulmonary arterial hypertension. These data suggest that CH is associated with increased endothelial nitric oxide synthase (eNOS) activity within the pulmonary arterial vasculature. In addition, the correlation of increased pulmonary arterial pressure with selectively enhanced arterial responsiveness to EDNO-mediated agonists suggests that arterial hypertension, rather than hypoxia per se, is a contributing factor in this response. Therefore, we hypothesized that 1) CH selectively upregulates eNOS within the pulmonary arterial vasculature and 2) monocrotaline (MC)-induced pulmonary arterial hypertension selectively enhances pulmonary arterial dilation to EDNO-dependent dilators and upregulates arterial eNOS. We examined the responses to the EDNO-dependent dilators arginine vasopressin and ionomycin in U-46619-constricted isolated perfused lungs from control and MC-treated rats. Microvascular pressure was assessed by the double-occlusion technique, allowing calculation of segmental resistances. Lungs from MC-treated rats exhibited augmented arterial dilation to arginine vasopressin compared with control lungs. However, the responses to ionomycin were not different between the two groups. Quantitative immunocytochemistry was used to compare pulmonary eNOS immunoreactivity in vessels from control, CH, and MC-treated rats. eNOS staining was more intense in the arteries of CH and NIC-treated rats compared with those of control animals, whereas CH and MC treatment had no effect on eNOS staining in veins. We conclude that pulmonary arterial hypertension, or altered vascular mechanical forces associated with hypertension, may be responsible for the augmented EDNO-dependent arterial dilation and upregulation of arterial eNOS in lungs from CH and MC-treated rats.