首页> 外文期刊>American Journal of Physiology >Angiotensin II stimulates nitric oxide production in pulmonary artery endothelium via the type 2 receptor.
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Angiotensin II stimulates nitric oxide production in pulmonary artery endothelium via the type 2 receptor.

机译:血管紧张素II通过2型受体刺激肺动脉内皮中一氧化氮的产生。

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We previously reported that angiotensin II stimulates an increase in nitric oxide production in pulmonary artery endothelial cells. The aims of this study were to determine which receptor subtype mediates the angiotensin II-dependent increase in nitric oxide production and to investigate the roles of the angiotensin type 1 and type 2 receptors in modulating angiotensin II-dependent vasoconstriction in pulmonary arteries. Pulmonary artery endothelial cells express both angiotensin II type 1 and type 2 receptors as assessed by RT-PCR, Western blot analysis, and flow cytometry. Treatment of the endothelial cells with PD-123319, a type 2 receptor antagonist, prevented the angiotensin II-dependent increase in nitric oxide synthase mRNA, protein levels, and nitric oxide production. In contrast, the type 1 receptor antagonist losartan enhanced nitric oxide synthase mRNA levels, protein expression, and nitric oxide production. Pretreatment of the endothelial cells with either PD-123319 or an anti-angiotensin II antibody prevented this losartan enhancement of nitric oxide production. Angiotensin II-dependent enhanced hypoxic contractions in pulmonary arteries were blocked by the type 1 receptor antagonist candesartan; however, PD-123319 enhanced hypoxic contractions in angiotensin II-treated endothelium-intact vessels. These data demonstrate that angiotensin II stimulates an increase in nitric oxide synthase mRNA, protein expression, and nitric oxide production via the type 2 receptor, whereas signaling via the type 1 receptor negatively regulates nitric oxide production in the pulmonary endothelium. This endothelial, type 2 receptor-dependent increase in nitric oxide may serve to counterbalance the angiotensin II-dependent vasoconstriction in smooth muscle cells, ultimately regulating pulmonary vascular tone.
机译:我们先前曾报道血管紧张素II刺激肺动脉内皮细胞中一氧化氮的产生增加。这项研究的目的是确定哪种受体亚型介导一氧化氮产生的血管紧张素II依赖性增加,并研究血管紧张素1型和2型受体在调节肺动脉血管紧张素II依赖性血管收缩中的作用。通过RT-PCR,Western印迹分析和流式细胞仪评估,肺动脉内皮细胞同时表达1型和2型血管紧张素受体。用2型受体拮抗剂PD-123319处理内皮细胞可防止血管紧张素II依赖性一氧化氮合酶mRNA,蛋白质水平和一氧化氮生成的增加。相反,1型受体拮抗剂氯沙坦可增强一氧化氮合酶的mRNA水平,蛋白质表达和一氧化氮生成。用PD-123319或抗血管紧张素II抗体对内皮细胞进行预处理可防止这种氯沙坦增强一氧化氮的产生。 1型受体拮抗剂坎地沙坦可阻断血管紧张素II依赖性增强的肺动脉缺氧收缩。然而,PD-123319增强了血管紧张素II处理的内皮完整血管中的低氧收缩。这些数据表明,血管紧张素II通过2型受体刺激一氧化氮合酶mRNA,蛋白质表达和一氧化氮生成的增加,而通过1型受体发出的信号负调控肺内皮细胞中一氧化氮的生成。内皮细胞中2型受体依赖性一氧化氮的增加可能有助于平衡平滑肌细胞中血管紧张素II依赖性血管收缩,最终调节肺血管张力。

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