Wilson C, Coldwell M C, Howlett D R, Cooper S M, Hamilton T C
Beecham Pharmaceuticals Research Division, Medicinal Research Centre, Essex, U.K.
Eur J Pharmacol. 1988 Aug 2;152(3):331-9. doi: 10.1016/0014-2999(88)90728-5.
Three agents with K+ channel blocking activity, procaine, 4-aminopyridine (4-AP) and tetraethylammonium (TEA), were tested for inhibition of vasorelaxation and 86Rb+ efflux induced by cromakalim (BRL 34915), pinacidil and nicorandil in rabbit isolated mesenteric artery. The potency order for inhibition of vasorelaxation was procaine greater than 4-AP greater than TEA and for inhibition of efflux was procaine = 4-AP greater than TEA. The K+ channel blockers did not discriminate between cromakalim, pinacidil or nicorandil on efflux but demonstrated preferential inhibition of vasorelaxation to cromakalim greater than pinacidil greater than nicorandil. In addition, the maximum response to cromakalim was depressed but that to pinacidil and nicorandil was not. The results confirm the role of K+ channel activation in vasorelaxation to cromakalim, pinacidil and nicorandil, but suggest that additional mechanisms may be involved for pinacidil and, in particular, for nicorandil.
对三种具有钾离子通道阻断活性的药物——普鲁卡因、4-氨基吡啶（4-AP）和四乙铵（TEA），进行了测试，观察其对兔离体肠系膜动脉中由克罗卡林（BRL 34915）、匹那地尔和尼可地尔诱导的血管舒张及86Rb+外流的抑制作用。抑制血管舒张的效力顺序为：普鲁卡因＞4-AP＞TEA；抑制外流的效力顺序为：普鲁卡因 = 4-AP＞TEA。钾离子通道阻滞剂对外流的抑制作用在克罗卡林、匹那地尔或尼可地尔之间无差异，但对血管舒张的抑制作用表现出对克罗卡林的优先抑制大于匹那地尔大于尼可地尔。此外，对克罗卡林的最大反应降低，但对匹那地尔和尼可地尔的最大反应未降低。结果证实了钾离子通道激活在对克罗卡林、匹那地尔和尼可地尔的血管舒张中的作用，但提示匹那地尔，尤其是尼可地尔可能涉及其他机制。
