Tirapelli Carlos R, Mingatto Fábio E, De Godoy Márcio A F, Ferreira Rosemary, De Oliviera Ana M
Department of Pharmacology, Faculty of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil.
Pharmacol Res. 2002 Dec;46(6):483-90. doi: 10.1016/s104366180200227x.
Vascular responses to hypoxia are heterogeneous and involve the release of vasodilators substances such as nitric oxide (NO) and prostacyclin (PGI(2)). In vitro studies have shown that Vitamin K(1) modulates the release of arachidonic acid (AA) in vascular cells, and thus inhibits the capacity of blood vessels to synthesise vasodilator AA metabolites. The aim of our work was to investigate the effects of Vitamin K(1) on the hypoxia-induced vasorelaxation. Hypoxia was induced by changing the gas from 95% O(2)/5% CO(2) to a mixture containing 95% N(2)/5% CO(2). Rat carotid arteries were pre-contracted with phenylephrine (Phe, 10(-8)mol/l) and when the contraction reached a plateau, the bath was bubbled with 95% N(2)/5% CO(2) for 15 min. In intact rings, there was a total relaxation after 15 min of exposure to hypoxia. Removal of the endothelium strongly reduced hypoxia-induced relaxation. In intact rings, indomethacin and L-NAME reduced the hypoxic relaxation after 5 min of exposure but not after 10 or 15 min. Exposure of endothelium-intact rings to Vitamin K(1) (5 x 10(-6) and 5 x 10(-5)mol/l), L-NAME+indomethacin as well as the combination of L-NAME+indomethacin+Vitamin K(1) reduced the hypoxic relaxation after 5 and 10 min of exposure but not after 15 min. At 5 x 10(-7)mol/l Vitamin K(1) did not attenuate hypoxia-induced relaxation. It was also found that Vitamin K(1) (5 x 10(-6) and 5 x 10(-5)mol/l) inhibited ACh-induced relaxation in normoxic conditions. These results show that the effect of Vitamin K(1) on attenuating hypoxia-induced vasorelaxation is concentration-dependent and probably related to its action on endothelial cells.
血管对缺氧的反应是异质性的，涉及一氧化氮（NO）和前列环素（PGI₂）等血管舒张物质的释放。体外研究表明，维生素K₁可调节血管细胞中花生四烯酸（AA）的释放，从而抑制血管合成血管舒张性AA代谢产物的能力。我们研究的目的是探讨维生素K₁对缺氧诱导的血管舒张的影响。通过将气体从95%O₂/5%CO₂改为含95%N₂/5%CO₂的混合气体来诱导缺氧。大鼠颈动脉用去氧肾上腺素（Phe，10⁻⁸mol/L）预收缩，当收缩达到平台期时，将浴槽用95%N₂/5%CO₂鼓泡15分钟。在完整血管环中，暴露于缺氧15分钟后出现完全舒张。去除内皮可强烈降低缺氧诱导的舒张。在完整血管环中，吲哚美辛和L - 精氨酸甲酯在暴露5分钟后可降低缺氧诱导的舒张，但在10或15分钟后则不然。将内皮完整的血管环暴露于维生素K₁（5×10⁻⁶和5×10⁻⁵mol/L）、L - 精氨酸甲酯 + 吲哚美辛以及L - 精氨酸甲酯 + 吲哚美辛 + 维生素K₁的组合中，在暴露5和10分钟后可降低缺氧诱导的舒张，但在15分钟后则不然。在5×10⁻⁷mol/L维生素K₁时，不会减弱缺氧诱导的舒张。还发现维生素K₁（5×10⁻⁶和5×10⁻⁵mol/L）在常氧条件下可抑制乙酰胆碱诱导的舒张。这些结果表明，维生素K₁减弱缺氧诱导的血管舒张的作用是浓度依赖性的，并且可能与其对内皮细胞的作用有关。
