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首页> 外文期刊>Pulmonary Circulation >Effects of Tetrahydrobiopterin Oral Treatment in Hypoxia-Induced Pulmonary Hypertension in Rat:
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Effects of Tetrahydrobiopterin Oral Treatment in Hypoxia-Induced Pulmonary Hypertension in Rat:

机译：四氢生物蝶呤口服治疗对低氧诱导的肺动脉高压的影响：

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Endothelial nitric oxide synthase (eNOS) plays a major role in maintaining pulmonary vascular homeostasis. Tetrahydrobiopterin (BH4), an essential cofactor that stabilizes the dimerization of eNOS and balances nitric oxide (NO) and superoxide production, may have therapeutic potential in pulmonary hypertension. In the isolated perfused lung, we demonstrated a direct effect of exogenous administration of BH4 on pulmonary NO production, leading to acute vasorelaxation during the plateau phase of hypoxia-induced pulmonary vasoconstriction. In the chronic hypoxia-induced pulmonary hypertension rat model, chronic BH4 oral administration attenuated the pressor response to hypoxia (mean pulmonary artery pressure ± standard error of the mean, 31.8 ± 0.5 mmHg at 100 mg/kg/day; placebo group, 36.3 ± 0.6 mmHg; P 0.05). During telemetric monitoring, right ventricular systolic pressure was reduced by approximately 50% after 1 week of BH4 treatment at 100 mg/kg/day. BH4 at 100 mg/kg/day reduced right ventricular hypertrophy (from 0.55 ± 0.01 to 0.50 ± 0.01; P 0.05) and pulmonary vascular muscularization (from 79.2% ± 2% to 65.2% ± 3%; P 0.01). BH4 treatment enhanced lung eNOS activity and reduced superoxide production, with a net increase in cyclic guanosine monophosphate levels. BH4 is effective in attenuating pulmonary hypertension in the hypoxic rat model when given as a rescue therapy.
机译：内皮型一氧化氮合酶（eNOS）在维持肺血管稳态方面起着重要作用。四氢生物蝶呤（BH4）是稳定eNOS的二聚化并平衡一氧化氮（NO）和超氧化物产生的必要辅助因子，在肺动脉高压中可能具有治疗潜力。在孤立的灌注肺中，我们证明了BH4的外源性给药对肺NO产生的直接作用，导致在缺氧诱导的肺血管收缩的平台期急性血管舒张。在慢性低氧引起的肺动脉高压大鼠模型中，长期口服BH4可减轻对低氧的升压反应（平均肺动脉压±100 mg / kg / day时的平均标准误为31.8±0.5 mmHg;安慰剂组为36.3± 0.6 mmHg; P <0.05）。在遥测监测期间，以100 mg / kg / day的BH4治疗1周后，右心室收缩压降低了约50％。 100 mg / kg / day的BH4减少右心室肥大（从0.55±0.01到0.50±0.01; P <0.05）和肺血管肌肉化（从79.2％±2％到65.2％±3％; P <0.01）。 BH4处理增强了肺eNOS活性并减少了过氧化物的产生，环鸟苷单磷酸水平有所增加。当给予抢救疗法时，BH4可有效减轻低氧大鼠模型中的肺动脉高压。

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