The effect of some alpha-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 mumol/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 mumol/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 mumol/l), a H1 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 mumol/l), a selective blocker of ATP-sensitive K+ channels in cardiac and pancreatic tissues, and phentolamine (1-10 mumol/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 mumol/l) applied. E-4031 (0.01-0.3 mumol/l), a sotalol derivative and one of the most selective blockers of the delayed rectifier current (Ik) in cardiac tissue, was a potent contractile agent when added to the rat portal vein in the same way as the alpha-adrenoceptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Schwietert
R
R
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
Wilhelm
D
D
Wilffert
B
B
Van Zwieten
P A
PA
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019329:Idazoxan; D066298:In Vitro Techniques; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D015221:Potassium Channels; D015016:Yohimbine; D000255:Adenosine Triphosphate; D011224:Prazosin; D019329:Idazoxan; D010646:Phentolamine