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Interaction between endogenous nitric oxide and carbon monoxide in the pathogenesis of hypoxic pulmonary hypertension

机译:内源性一氧化氮与一氧化碳之间的相互作用在低氧性肺动脉高压的发病机理中的作用

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The aim of the study was to investigate the interaction between nitric oxygenase (NOS)/ nitric oxide (NO) and heme oxygenase (HO)/ carbon monoxide (CO) system in the pathogenesis of hypoxic pulmonary hypertension. On a rat model of hypoxic pulmonary hypertension, the pulmonary artery pressure was measured, and NO formation and expression of NOS in pulmonary tissues were examined after treatment with ZnPP-IX, an HO-1 inhibitor. The pulmonary artery pressure, CO formation and expression of HO-1 in pulmonary tissues were examined after treatment with L-NAME, a NOS inhibitor. We found that pulmonary hypertension developed after 2-week hypoxia, while the concentration of NO in the pulmonary tissue homogenates and the expression of NOS in intrapulmonary artery endothelial cells decreased markedly. ZnPP-IX worsened pulmonary hypertension of hypoxic rats. However, it increased endogenous production of NO and the expression of NOS obviously. The concentration of CO in the pulmonary tissue homogenates and the expression of HO-1 in intrapulmonary artery smooth muscle cells increased markedly with hypoxic pulmonary hypertension. L-NAME worsened pulmonary hypertension of hypoxic rats, but inhibited CO formation and HO-1 expression (P < 0.01). The results of this study suggested that endogenous NOS/NO and HO/CO systems might interact with each other and therefore play an important regulating role in hypoxic pulmonary hypertension.
机译:该研究的目的是研究在低氧性肺动脉高压的发病机制中一氧化氮酶(NOS)/一氧化氮(NO)与血红素氧化酶(HO)/一氧化碳(CO)系统之间的相互作用。在低氧性肺动脉高压的大鼠模型中,测量肺动脉压,并用HO-1抑制剂ZnPP-IX处理后检查肺组织中NO的形成和NOS的表达。用NOS抑制剂L-NAME处理后,检查肺动脉压力,CO形成和肺组织HO-1的表达。我们发现缺氧2周后发生了肺动脉高压,而肺组织中的NO浓度均匀,肺内动脉内皮细胞中的NOS表达明显降低。 ZnPP-IX加重了缺氧大鼠的肺动脉高压。但是,它明显增加了NO的内源性产生和NOS的表达。低氧性肺动脉高压导致肺组织匀浆中CO浓度升高,肺内动脉平滑肌细胞中HO-1的表达明显增加。 L-NAME加重了低氧大鼠的肺动脉高压,但抑制了CO的形成和HO-1的表达(P <0.01)。这项研究的结果表明内源性NOS / NO和HO / CO系统可能相互影响,因此在低氧性肺动脉高压中起重要的调节作用。

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