Corriu C, Félétou M, Puybasset L, Bea M L, Berdeaux A, Vanhoutte P M
Département de Diabétologie, Institut de Recherches Servier, Suresnes, France.
J Cardiovasc Pharmacol. 1998 Dec;32(6):944-50. doi: 10.1097/00005344-199812000-00011.
To study the effects of chronic in vivo inhibition of NO synthase on endothelium-dependent hyperpolarization, cell-membrane potential (in individual vascular smooth-muscle cells) and changes in tension (in isolated rings) were recorded from isolated canine coronary arteries and guinea-pig carotid arteries and aortas. In coronary arteries taken from control dogs and contracted with U46619, acetylcholine- and bradykinin-induced endothelium-dependent relaxations, which were unaffected by short-term in vitro exposure to indomethacin but were inhibited partially by L-nitro-arginine (LNA). In coronary arteries taken from dogs treated over the long term in vivo with LNA (30 mg/kg on the first day and 20 mg/kg the 7 following days, i.v.), the response to acetylcholine and bradykinin was inhibited when compared with arteries from control dogs. Short-term in vitro exposure to LNA or indomethacin or both did not influence the effects of either agonist. In these arteries, the hyperpolarizing response to acetylcholine, observed in the presence of LNA and indomethacin, was enhanced, whereas that to bradykinin was partially inhibited. In the guinea pig isolated aorta, the relaxation to bradykinin was abolished by long-term in vivo treatment with L-nitro-arginine-methyl-ester (L-NAME; 1.5 mg/ml, in the drinking water for > or =4 days). In the isolated guinea pig carotid artery studied in the presence of LNA and indomethacin, acetylcholine induced a hyperpolarization that was not significantly affected by long-term in vivo treatment with L-NAME. These findings indicate that endothelium-dependent hyperpolarizations are maintained during long-term inhibition of NO synthase and probably act as a back-up mechanism to elicit endothelium-dependent relaxations.
为研究慢性体内抑制一氧化氮合酶对内皮依赖性超极化的影响，从离体犬冠状动脉、豚鼠颈动脉和主动脉记录了（单个血管平滑肌细胞中的）细胞膜电位和（离体血管环中的）张力变化。在取自对照犬并经U46619收缩的冠状动脉中，乙酰胆碱和缓激肽诱导的内皮依赖性舒张不受短期体外吲哚美辛暴露的影响，但部分受到L-硝基精氨酸（LNA）的抑制。在长期体内用LNA（第一天30mg/kg，随后7天每天20mg/kg，静脉注射）处理的犬的冠状动脉中，与对照犬的动脉相比，对乙酰胆碱和缓激肽的反应受到抑制。短期体外暴露于LNA或吲哚美辛或两者均不影响任何一种激动剂的作用。在这些动脉中，在LNA和吲哚美辛存在下观察到的对乙酰胆碱的超极化反应增强，而对缓激肽的反应则部分受到抑制。在豚鼠离体主动脉中，长期体内用L-硝基精氨酸甲酯（L-NAME；1.5mg/ml，饮用水中≥4天）处理可消除对缓激肽的舒张反应。在存在LNA和吲哚美辛的情况下研究的离体豚鼠颈动脉中，乙酰胆碱诱导的超极化不受长期体内L-NAME处理的显著影响。这些发现表明，在长期抑制一氧化氮合酶期间，内皮依赖性超极化得以维持，并且可能作为引发内皮依赖性舒张的备用机制。
