The effect of some α-adrenoceptor antagonists on spontaneous myogenic activity in the rat portal vein and the putative involvement of ATP-sensitive K+ channels

In the present study we showed that the alpha-adrenoceptor antagonists phentolamine, yohimbine, prazosin, corynanthine and idazoxan, when cumulatively applied in high concentrations (1-100-mu-mol/l), can increase spontaneous myogenic activity in the rat portal vein. 5-Methyl-urapidil and rauwolscine were ineffective in this respect. Pretreatment with phenoxybenzamine in a concentration of 1-mu-mol/l (20 min), which results in alkylation of all functional alpha-adrenoceptors in the rat portal vein, was unable to antagonize the increase in spontaneous myogenic activity elicited by phentolamine. Antazoline (1-100-mu-mol/l), a H-1 antagonist and 2-substituted imidazoline which is devoid of alpha-adrenoceptor blocking properties, exhibited similar effects on spontaneous myogenic activity as its structurally closely related analogue phentolamine. Since phentolamine is reported to interact with ATP-sensitive K+ channels we investigated the role of K+ channels in more detail. The K+ channel openers cromakalim and diazoxide elicited a decrease in spontaneous myogenic activity. Glibenclamide (0.3-3-mu-mol/l), a selective blocker of ATP-sensitive K+ channels in cardiac and pancreatic tissues, and phentolamine (1-10-mu-mol/l) shifted the concentration-response curves of cromakalim and diazoxide concentration dependently to the right. Yohimbine showed only a modest effect in the highest concentration (100-mu-mol/l) applied. E-4031 (0.01-0.3-mu-mol/l), a sotalol derivative and one of the most selective blockers of the delayed rectifier current (I(k)) in cardiac tissue, was a potent contractile agent when added to the rat portal vein in the same way as the alpha-adrenoceptor antagonists. All other alpha-adrenoceptor antagonists as well as E-4031, when tested in concentrations which maximally stimulated spontaneous myogenic activity, failed to influence the relaxations induced by cromakalim and diazoxide. The results of the present study cannot be explained on the basis of alpha-adrenoceptor blockade. Phentolamine, in contrast to the other alpha-adrenoceptor antagonists, can block glibenclamide-sensitive K+ channels in the rat portal vein. However, it seems unlikely that this property can explain its potent effects on spontaneous myogenic activity, since glibenclamide itself was inactive.