Kreye V A, Lenz T, Pfründer D, Theiss U
Second Department of Physiology, University of Heidelberg, Germany.
J Cardiovasc Pharmacol. 1992;20 Suppl 3:S8-12. doi: 10.1097/00005344-199206203-00003.
Nicorandil and cromakalim were found to stimulate 86Rb efflux (a marker of K+ ions) from resting preparations of rabbit aorta. This action was suppressed by 10(-5) M glibenclamide, an antagonist of K(+)-channel openers in vascular smooth muscle. Through intracellular production of cyclic GMP, and subsequent suppression of cellular Ca2+ activation, nitrovasodilators interfere indirectly with the activation of Ca(2+)-dependent ion channels. 8-Bromo-cyclic GMP and sodium nitroprusside antagonized the Ca(2+)-dependent 86Rb efflux induced by 3 x 10(-7) M norepinephrine. When nicorandil and cromakalim were investigated in the same experimental setup in the presence of glibenclamide to suppress stimulation of K+ channels, only nicorandil also suppressed the norepinephrine-induced increase of the 86Rb efflux. These results confirm that nicorandil acts as both an opener of K+ channels and a nitrovasodilator. Nicorandil relaxed helical strips from rabbit aorta contracted by 10(-7) M norepinephrine, but in contrast to the relaxant action of cromakalim, this response was not antagonized by the use of glibenclamide, indicating a greater importance of the nitrovasodilator mechanism than of the K(+)-channel-opening activity for relaxation in this tissue. However, when the nitrate-like action of nicorandil was suppressed by 10(-5) M methylene blue, the K(+)-channel-opening activity was unmasked on addition of 10(-4) M glibenclamide at high concentrations of nicorandil.
已发现尼可地尔和克罗卡林可刺激家兔主动脉静息标本中的⁸⁶Rb外流（钾离子的一种标志物）。血管平滑肌中钾通道开放剂的拮抗剂10⁻⁵M格列本脲可抑制此作用。通过细胞内环鸟苷酸的产生以及随后对细胞内钙离子激活的抑制，硝基血管扩张剂间接干扰钙依赖性离子通道的激活。8-溴环鸟苷酸和硝普钠可拮抗3×10⁻⁷M去甲肾上腺素诱导的钙依赖性⁸⁶Rb外流。当在存在格列本脲以抑制钾通道刺激的相同实验装置中研究尼可地尔和克罗卡林时，只有尼可地尔也抑制了去甲肾上腺素诱导的⁸⁶Rb外流增加。这些结果证实尼可地尔兼具钾通道开放剂和硝基血管扩张剂的作用。尼可地尔可使由10⁻⁷M去甲肾上腺素收缩的家兔主动脉螺旋条舒张，但与克罗卡林的舒张作用相反，这种反应不会被格列本脲拮抗，表明在该组织中，硝基血管扩张剂机制对舒张的重要性大于钾通道开放活性。然而，当尼可地尔的硝酸盐样作用被10⁻⁵M亚甲蓝抑制时，在高浓度尼可地尔存在下加入10⁻⁴M格列本脲时，钾通道开放活性会被揭示出来。
