Bray K, Quast U
Preclinical Research, Sandoz Pharma Ltd., Basel, Switzerland.
Naunyn Schmiedebergs Arch Pharmacol. 1991 Sep;344(3):351-9. doi: 10.1007/BF00183011.
The effects of the K+ channel opening drugs minoxidil sulphate and cromakalim, on 42K+ and 86Rb+ efflux and on vasorelaxation in rat isolated aorta, were compared. In rat aortic rings precontracted with noradrenaline (100 nmol/l), minoxidil sulphate and cromakalim concentration-dependently inhibited induced tension by up to 90%, with pD2 values of 7.35 +/- 0.1 and 7.17 +/- 0.1, respectively. Glibenclamide (300 nmol/l), produced 2200- and 19-fold rightward shifts in the concentration-relaxation curves to minoxidil sulphate and cromakalim, respectively, without an effect on the maximum relaxation. Both minoxidil sulphate and cromakalim increased the efflux of 42K+ and 86Rb+ from aorta in a concentration-dependent manner, with midpoints in the mumol/l range; the maximum efflux induced by minoxidil sulphate being approximately one tenth of that induced by cromakalim. The ratio of stimulated 86Rb+/42K+ efflux increased from 0.22 to 0.48 with increasing cromakalim concentrations, but was approximately constant (approximately 0.39) when the minoxidil sulphate concentration was varied. In the presence of minoxidil sulphate, the effects of cromakalim on 42K+ and 86Rb+ efflux were inhibited in a concentration-dependent manner, by up to 60%. In the continuing presence of cromakalim (300 nmol/l), minoxidil sulphate (10 mumol/l)-induced increases in 42K+ and 86Rb+ efflux were inhibited by 45%, whereas conditioning with cromakalim (1 mumol/l) inhibited the 86Rb+ efflux stimulated by additional superfusion of cromakalim (1 mumol/l) by 85%. Glibenclamide inhibited minoxidil sulphate (10 mumol/l)- and cromakalim (1 mumol/l)-induced increases in 42K+ and 86Rb+ efflux in a concentration-dependent manner with IC50 values of approximately 80 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)
比较了钾通道开放药物硫酸米诺地尔和克罗卡林对大鼠离体主动脉中42K+和86Rb+外流以及血管舒张的影响。在去甲肾上腺素（100 nmol/l）预收缩的大鼠主动脉环中，硫酸米诺地尔和克罗卡林浓度依赖性地抑制诱导张力，最高可达90%，pD2值分别为7.35±0.1和7.17±0.1。格列本脲（300 nmol/l）使硫酸米诺地尔和克罗卡林的浓度-舒张曲线分别向右移动2200倍和19倍，而对最大舒张无影响。硫酸米诺地尔和克罗卡林均以浓度依赖性方式增加主动脉中42K+和86Rb+的外流，中点在μmol/l范围内；硫酸米诺地尔诱导的最大外流约为克罗卡林诱导的最大外流的十分之一。随着克罗卡林浓度的增加，刺激的86Rb+/42K+外流比值从0.22增加到0.48，但当硫酸米诺地尔浓度变化时，该比值大致恒定（约0.39）。在硫酸米诺地尔存在的情况下，克罗卡林对42K+和86Rb+外流的影响以浓度依赖性方式被抑制，最高可达60%。在持续存在克罗卡林（300 nmol/l）的情况下，硫酸米诺地尔（10 μmol/l）诱导的42K+和86Rb+外流增加被抑制45%，而用克罗卡林（1 μmol/l）预处理可抑制额外灌注克罗卡林（1 μmol/l）刺激的86Rb+外流的85%。格列本脲以浓度依赖性方式抑制硫酸米诺地尔（10 μmol/l）和克罗卡林（1 μmol/l）诱导的42K+和86Rb+外流增加，IC50值约为80 nmol/l。（摘要截断于250字）
