Effects of imidazoline-related compounds on the mechanical response to nicorandil in the rat portal vein.
The purpose of this study was to investigate the interactions of compounds structurally related to imidazoline at K+ channels located in the rat portal vein. Nicorandil, a K+ channel activator, dose dependently inhibited spontaneous contractions of the isolated rat portal vein. Glibenclamide (0.1-1 microM), an ATP-sensitive K+ channel blocker, competitively antagonized the response to nicorandil, whereas methylene blue (10 microM), a guanylate cyclase inhibitor, did not. Phentolamine, antazoline, tolazoline, and midaglizole also shifted the dose-response curve for nicorandil to the right in the dose range of 1-100 microM. The rank order of potency was glibenclamide much greater than phentolamine = antazoline = midaglizole greater than tolazoline. In contrast, clonidine, idazoxan, imidazole, 1-benzylimidazole, and yohimbine were ineffective. In addition, cromakalim (1-100 nM), a selective K+ channel activator, also inhibited spontaneous contractions of the rat portal vein, and this effect was antagonized by phentolamine in a similar way to that found with nicorandil. These results suggest that some 2-substituted imidazolines, including phentolamine, possibly act as K+ channel blockers, like glibenclamide, in vascular smooth muscle.
Okumura
K
K
Research Laboratories, Maruko Pharmaceutical Co., Ltd., Aichi, Japan.
Ichihara
K
K
Nagasaka
M
M
D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019806:Cromakalim; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020108:Nicorandil; D011169:Portal Vein / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D001578:Benzopyrans; D007093:Imidazoles; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil