Effects of K+ channel blockers on the relaxant action of dihydralazine, cromakalim and nitroprusside in isolated rabbit femoral arteries.
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 (EC50 = 1.1 microM; Emax = 95%) and relaxed the contractions elicited by 20 mM K+ (EC50 = 2.0 microM; Emax = 81% in preference to 124 mM K(+)-induced contractions (EC50 = 30.1 microM; Emax = 54%). Cromakalim, but not nitroprusside, also selectively relaxed 20 mM K(+)-induced contractions. In noradrenaline-contracted arteries, glibenclamide (10 microM) 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 Ba2+ (0.1 mM), 4-aminopyridine (5 mM) and procaine (0.1 mM) failed to influence dihydralazine-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.
Thirstrup
S
S
Institute of Pharmacology, University of Aarhus, Denmark.
Nielsen-Kudsk
J E
JE
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004078:Dihydralazine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D009599:Nitroprusside; D004078:Dihydralazine; D009638:Norepinephrine