Tirapelli Carlos R, Mingatto Fábio E, de Oliveira Ana M
Department of Pharmacology, Faculty of Medicine, University of São Paulo, Brazil.
Pharmacology. 2002 Sep;66(1):36-43. doi: 10.1159/000063255.
The purpose of the present study was to investigate the effects of vitamin K(1) on vascular smooth muscle contractility in response to phenylephrine (Phe) during hypoxia. Rat carotid rings were placed in an organ chamber containing Krebs' solution. The rings were subjected to hypoxia by changing the gas from 95% O(2):5% CO(2) to a mixture containing 95% N(2):5% CO(2). Concentration response curves for Phe were determined before, during, and after exposure to hypoxia. Endothelium-intact rings were incubated with vitamin K(1) for 10 min in normoxic conditions before being subjected to hypoxia. In another set of experiments, endothelium-intact rings were incubated with N(G)-nitro-L-arginine methyl ester (L-NAME), indomethacin or a combination of these drugs for 30 min. In endothelium-intact rings, hypoxia caused significant reductions in E(max) (from 0.97 +/- 0.03 to 0.61 +/- 0.04 g/mg; mean +/- SEM) and pD(2) values (from 8.26 +/- 0.07 to 7.67 +/- 0.10). Removal of a functional endothelium effectively prevented the hypoxia-induced reduction in E(max) values, but not in pD(2) values (from 9.14 +/- 0.10 to 8.70 +/- 0.11). Pretreatment with vitamin K(1) at 3 concentrations (5 x 10(-8), 5 x 10(-7), 5 x 10(-6) mol/l) prevented the inhibitory effect of hypoxia in intact rings. Exposure of endothelium-intact rings to L-NAME plus indomethacin also inhibited the hypoxic effect. Our results show that vitamin K(1) prevents the deleterious vascular effects induced by hypoxia, probably due to its action on endothelial cells.
本研究的目的是调查维生素K(1)对缺氧期间去氧肾上腺素（Phe）引起的血管平滑肌收缩性的影响。将大鼠颈动脉环置于含有 Krebs 溶液的器官浴槽中。通过将气体从95% O(2):5% CO(2) 更换为含有95% N(2):5% CO(2) 的混合物使颈动脉环处于缺氧状态。在缺氧暴露前、期间和之后测定Phe的浓度-反应曲线。在常氧条件下，将完整内皮的血管环与维生素K(1) 孵育10分钟，然后再进行缺氧处理。在另一组实验中，将完整内皮的血管环与N(G)-硝基-L-精氨酸甲酯（L-NAME）、吲哚美辛或这些药物的组合孵育30分钟。在完整内皮的血管环中，缺氧导致E(max) 显著降低（从0.97±0.03降至0.61±0.04 g/mg；平均值±标准误）和pD(2) 值降低（从8.26±0.07降至7.67±0.10）。去除功能性内皮可有效防止缺氧诱导的E(max) 值降低，但不能防止pD(2) 值降低（从9.14±0.10降至8.70±0.11）。用3种浓度（5×10(-8)、5×(-7)、5×10(-6) mol/l）的维生素K(1) 预处理可防止缺氧对完整血管环的抑制作用。将完整内皮的血管环暴露于L-NAME加吲哚美辛也可抑制缺氧效应。我们的结果表明，维生素K(1) 可防止缺氧诱导的有害血管效应，这可能是由于其对内皮细胞的作用。
