Jovanović A, Grbović L, Jovanović S
Department of Pharmacology, Medical Faculty, Belgrade, Yugoslavia.
Eur J Pharmacol. 1995 Jun 23;280(1):95-100. doi: 10.1016/0014-2999(95)00236-e.
The effect of K+ channel blockers on acetylcholine-induced relaxation in guinea-pig uterine arterial rings was investigated. Acetylcholine (0.1 nM-60 microM) induced endothelium-dependent relaxation of phenylephrine-precontracted guinea-pig uterine artery. Methylene blue (30 nM-1 microM) and NG-monomethyl-L-arginine (3-30 microM) antagonized the effect of acetylcholine, with suppression of the maximal acetylcholine-induced relaxation, in a concentration-dependent manner. The inhibition of relaxation by NG-monomethyl-L-arginine (10 microM) was significantly overcome by L-arginine (10 microM), but not by D-arginine (100 microM). In contrast, the administration of K+ channel blockers, tetraethylammonium (6 mM), glibenclamide (5 microM), apamin (1 microM) and 4-aminopyridine (1 mM), did not modify the relaxation of guinea-pig uterine artery induced by acetylcholine. The concomitant addition of K+ channel blockers in the same concentrations also did not alter the inhibition of acetylcholine-induced relaxation produced by NG-monomethyl-L-arginine (30 microM). Finally, the acetylcholine-evoked relaxations were unaltered when K(+)-rich Krebs-Ringer-bicarbonate solution was used to induce tone instead of phenylephrine. Indomethacin (10 microM) and diethylcarbamazine (100 microM) had no effects on acetylcholine-induced relaxation. These findings indicate that K+ channels are probably not involved in the endothelium-dependent guinea-pig uterine arterial relaxation elicited by acetylcholine.
研究了钾通道阻滞剂对豚鼠子宫动脉环中乙酰胆碱诱导的舒张作用。乙酰胆碱（0.1 nM - 60 μM）可诱导苯肾上腺素预收缩的豚鼠子宫动脉产生内皮依赖性舒张。亚甲蓝（30 nM - 1 μM）和N - 单甲基 - L - 精氨酸（3 - 30 μM）以浓度依赖性方式拮抗乙酰胆碱的作用，抑制乙酰胆碱诱导的最大舒张。L - 精氨酸（10 μM）可显著克服N - 单甲基 - L - 精氨酸（10 μM）对舒张的抑制作用，但D - 精氨酸（100 μM）则不能。相反，给予钾通道阻滞剂四乙铵（6 mM）、格列本脲（5 μM）、蜂毒明肽（1 μM）和4 - 氨基吡啶（1 mM），并未改变乙酰胆碱诱导的豚鼠子宫动脉舒张。同时加入相同浓度的钾通道阻滞剂也未改变N - 单甲基 - L - 精氨酸（30 μM）对乙酰胆碱诱导舒张的抑制作用。最后，当用富含钾的 Krebs - Ringer - 碳酸氢盐溶液代替苯肾上腺素诱导张力时，乙酰胆碱诱发的舒张未发生改变。吲哚美辛（10 μM）和乙胺嗪（100 μM）对乙酰胆碱诱导的舒张无影响。这些发现表明，钾通道可能不参与乙酰胆碱引起的豚鼠子宫动脉内皮依赖性舒张。
