Sepiapterin decreases vasorelaxation in nitric oxide synthase inhibition-induced hypertension.
Sepiapterin decreases vasorelaxation in nitric oxide synthase inhibition-induced hypertension.
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Sepiapterin 可减少一氧化氮合酶抑制引起的高血压的血管舒张作用。
DOI：
10.1097/00005344-200401000-00014
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发表时间：
2004
影响因子：
3
通讯作者：
Webb,RClinton
中科院分区：
文献类型：
--
作者：
Mitchell,BrettM;Dorrance,AnneM;Ergul,Adviye;Webb,RClinton
外源性BH 4（四氢生物蝶呤）已被证明可以改善心血管疾病的内皮功能;然而，在超氧化物水平升高和一氧化氮合酶（NOS）活性降低的情况下，BH 4可能会自动氧化，导致血管舒张减少。作者验证了这一假设，即增加BH 4将进一步减少NOS抑制引起高血压大鼠血管内皮依赖性舒张。N ω-硝基-L-精氨酸（L-NNA，约49 mg/kg/d）经饮水给药4 d。尾袖技术测量的收缩压在l-NNA处理的大鼠中显著增加。将内皮完整的主动脉段分离并悬挂在器官室中，用于测量等长力产生。与对照组相比，L-NNA处理大鼠的主动脉对乙酰胆碱的松弛降低，并且在与sepiapterin孵育后进一步降低。超氧化物歧化酶（SOD）恢复松弛从l-NNA处理的大鼠到对照组。此外，SOD或抗坏血酸逆转了sepiapterin诱导的L-NNA处理的大鼠腹主动脉舒张减少。与未处理的对照组相比，在存在和不存在sepiapterin的情况下，来自l-NNA处理的大鼠的主动脉以及sepiapterin处理的对照主动脉的超氧化物的二氢乙锭染色增加。这些结果支持以下假设：在NOS抑制的情况下，sepiapterin进一步降低血管舒张，并且可能由BH 4自氧化引起。
Exogenous BH4 (tetrahydrobiopterin) has been shown to improve endothelial function in cardiovascular disease; however, in the presence of elevated superoxide levels and decreased nitric oxide synthase (NOS) activity, BH4 may become autoxidized, resulting in reduced vasodilation. The authors tested the hypothesis that increasing BH4 will further reduce endothelium-dependent relaxation in aortas from rats made hypertensive by NOS inhibition. N ω-nitro-L-arginine (L-NNA, approximately 49 mg/kg/d) was administered in the rats' drinking water for 4 days. Systolic blood pressures, measured by tail-cuff technique, were significantly increased in l-NNA–treated rats. Endothelium-intact aortic segments were isolated and hung in organ chambers for the measurement of isometric force generation. Aortas from l-NNA–treated rats had decreased relaxation to acetylcholine compared with controls, and this was further decreased after incubation with sepiapterin. Superoxide dismutase (SOD) restored relaxation in aortas from l-NNA–treated rats to that of control. In addition, SOD or ascorbic acid reversed the sepiapterin-induced decrease in relaxation in aortas from l-NNA treated rats. Aortas from l-NNA–treated rats in the absence and presence of sepiapterin, and sepiapterin-treated control aortas, had increased dihydroethidium staining for superoxide compared with untreated controls. These results support the hypothesis that sepiapterin further reduces vasodilation in the presence of NOS inhibition and may be caused by BH4 autoxidation.