一氧化氮和钾离子通道激活对普鲁卡因诱导的离体大鼠主动脉血管舒张的作用。
Contribution of nitric oxide and K+ channel activation to vasorelaxation of isolated rat aorta induced by procaine.
作者信息
Huang Y, Lau C W, Chan F L, Yao X Q
机构信息
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, NT.
出版信息
Eur J Pharmacol. 1999 Feb 19;367(2-3):231-7. doi: 10.1016/s0014-2999(98)00950-9.
The endothelium-dependent and -independent relaxant effect of procaine was examined in isolated rat aortic rings. Procaine induced relaxation of arteries precontracted with phenylephrine or with 60 mM K+ in a concentration-dependent manner (0.01-3 mM). Procaine (1 mM) inhibited the transient contraction induced by caffeine (10 mM) in Ca2+-free Krebs solution. Removal of the endothelium caused a rightward shift of the concentration-response curve for procaine. N(G)-Nitro-L-arginine (L-NNA, 10-100 microM), N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microM) and methylene blue (1-10 microM) significantly attenuated the procaine-induced relaxation without affecting the maximal response. L-Arginine (1 mM) partially but significantly antagonized the effect of L-NAME (100 microM). Pretreatment of endothelium-intact aortic rings with procaine (1 mM) or with acetylcholine (10 microM) significantly elevated the tissue contents of cyclic GMP and this increase was inhibited in the presence of 100 microM L-NNA. Tetrapentylammonium ions (1-3 microM) reduced the procaine-induced relaxation in both endothelium-intact and -denuded arteries. Tetrapentylammonium ions (3 microM) did not affect the procaine-induced relaxation of 60 mM K+-contracted arteries. Tetraethylammonium ions (3 mM) inhibited the procaine-induced relaxation. In contrast, iberiotoxin (100 nM), glibenclamide (3 microM), 4-aminopyridine (3 mM) and indomethacin (10 microM) had no effect. These results indicate that the procaine-induced relaxation may be mediated through multiple mechanisms. A substantial portion of the procaine-induced relaxation in rat aorta was caused by nitric oxide but not by other endothelium-derived factors. The activation of tetrapentylammonium- and tetraethylammonium-sensitive K+ channels contributes in part to the procaine-induced vasorelaxation. Besides, procaine may directly inhibit both external Ca2+ entry and internal Ca2+ release in aortic smooth muscle cells.
在离体大鼠主动脉环中检测了普鲁卡因的内皮依赖性和非依赖性舒张作用。普鲁卡因以浓度依赖性方式（0.01 - 3 mM）诱导由去氧肾上腺素或60 mM K⁺预收缩的动脉舒张。在无钙的Krebs溶液中，普鲁卡因（1 mM）抑制了咖啡因（10 mM）诱导的瞬时收缩。去除内皮导致普鲁卡因浓度 - 反应曲线右移。N(G)-硝基-L-精氨酸（L-NNA，10 - 100 microM）、N(G)-硝基-L-精氨酸甲酯（L-NAME，100 microM）和亚甲蓝（1 - 10 microM）显著减弱了普鲁卡因诱导的舒张，而不影响最大反应。L-精氨酸（1 mM）部分但显著拮抗L-NAME（100 microM）的作用。用普鲁卡因（1 mM）或乙酰胆碱（10 microM）预处理内皮完整的主动脉环可显著提高环磷酸鸟苷的组织含量，并且在存在100 microM L-NNA的情况下这种增加受到抑制。四戊铵离子（1 - 3 microM）降低了内皮完整和去内皮动脉中普鲁卡因诱导的舒张。四戊铵离子（3 microM）不影响普鲁卡因对60 mM K⁺收缩动脉的舒张作用。四乙铵离子（3 mM）抑制了普鲁卡因诱导的舒张。相反，iberiotoxin（100 nM）、格列本脲（3 microM）、4-氨基吡啶（3 mM）和吲哚美辛（10 microM）没有作用。这些结果表明，普鲁卡因诱导的舒张可能通过多种机制介导。大鼠主动脉中普鲁卡因诱导的舒张很大一部分是由一氧化氮引起的，而非其他内皮衍生因子。四戊铵和四乙铵敏感的钾通道的激活部分促成了普鲁卡因诱导的血管舒张。此外，普鲁卡因可能直接抑制主动脉平滑肌细胞中外源性Ca²⁺内流和内源性Ca²⁺释放。
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