Effects of imidazoline-related compounds on the mechanical response to nicorandil in the rat portal vein

Abstract

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 μM), an ATP-sensitive K + channel blocker, competitively antagonized the response to nicorandil, whereas methylene blue (10 μM), 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 μM. The rank order of potency was glibenclamide >phentolamine = antazoline = midaglizole > 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.