Effects of K + channel blockers on the relaxant action of dihydralazine, cromakalim and nitroprusside in isolated rabbit femoral arteries

Abstract

The relaxant responses to dihydralazine and the influence of different K + channel blockers were studied in isolated rabbit femoral arteries. The prototype K + channel opener, cromakalim, and nitroprusside, which does not produce relaxation by K + channel activation were used for comparison. Dihydralazine was most effective on contractions induced by noradrenaline (EC 50 = 1.1 μM; E max = 95%) and relaxed the contractions elicited by 20 mM K + (EC 50 = 2.0 μM; E max = 81% in preference to 124 mM K +-induced contractions (EC 50 = 30.1 μM; E max = 54%). Cromakalim, but not nitroprusside, also selectively relaxe 20 mM K +-induced contractions. In noradrenaline-contracted arteries, glibenclamide (10 μM) completely suppressed the relaxant response to cromakalim but did not influence the vasorelaxation produced by dihydralazine or nitroprusside. Tetraethylammonium (8 mM) and Cs + (4 mM) shifted the concentration-relaxation curve for dihydralazine 2-fold to the right, whereas Ba 2+ (0.1 mM), 4-aminopyridine (5 mM) and procaine (0.1 mM) failed to influence dihydralzine-induced responses. Tetraethylammonium (8 mM) shifted the concentration-relaxation curve for cromakalim and nitroprusside 6-fold to the right and suppressed the maximal relaxant effects by about 30%. It is concluded that dihydralazine produces vascular smooth muscle relaxation by a mechanism different from the opening of glibenclamide- and ATP-sensitive K + channels.