Search

In the present study we showed that the α-adrenoceptor antagonists phentolamine, yohimbine, prazosin, corynanthine and idazoxan, when cumulatively applied in high concentrations (1-100 μmol/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 μmol/l (20 min), which results in alkylation of all functional α-adrenoceptors in the rat portal vein, was unable to antagonize the increase in spontaneous myogenic activity elicited by phentolamine. Antazoline (1-100 μmol/l), a H1antagonist and 2-substituted imidazoline which is devoid of α-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 μmol/l), a selective blocker of ATP-sensitive K+channels in cardiac and pancreatic tissues, and phentolamine (1-10 μmol/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 μmol/l) applied. E-4031 (0.01-0.3 μmol/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 α-adrenoceptor antagonists. All other α-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 α-adrenoceptor blockade. Phentolamine, in contrast to the other α-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.

In the present study we showed that the α-adrenoceptor antagonists phentolamine, yohimbine, prazosin, corynanthine and idazoxan, when cumulatively applied in high concentrations (1-100 μmol/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 μmol/l (20 min), which results in alkylation of all functional α-adrenoceptors in the rat portal vein, was unable to antagonize the increase in spontaneous myogenic activity elicited by phentolamine. Antazoline (1-100 μmol/l), a H1antagonist and 2-substituted imidazoline which is devoid of α-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 μmol/l), a selective blocker of ATP-sensitive K+channels in cardiac and pancreatic tissues, and phentolamine (1-10 μmol/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 μmol/l) applied. E-4031 (0.01-0.3 μmol/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 α-adrenoceptor antagonists. All other α-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 α-adrenoceptor blockade. Phentolamine, in contrast to the other α-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.