Sensitivity of alpha-adrenoceptor agonists to the calcium channel activator, Bay K 8644, in canine saphenous vein.
The purpose of the present study was to determine if the calcium channel activator, Bay K 8644, enhances the vasoconstrictor actions of selective alpha 1- and alpha 2-adrenoceptor agonists in canine saphenous vein. Phenylephrine (PE) and St 587 were used as fully and partially selective alpha 1-adrenoceptor agonists, B-HT 920 and B-HT 958 were used as fully and partially selective alpha 2-adrenoceptor agonists. Bay K 8644 (10(-8) M) markedly potentiated B-HT-958-mediated vasoconstrictor responses with a leftward shift and an increase in the maximum response of the logarithmic dose-response curve. Bay K 8644 produced less potentiation of responses to B-HT 920 and had minimal effects on responses to St 587 and PE. The intrinsic activities of the alpha-adrenoceptor agonists, as compared to the maximum response obtained by norepinephrine, in decreasing order, were PE greater than St 587 greater than B-HT 920 greater than B-HT 958, whereas the susceptibility of alpha-adrenoceptor agonists to potentiation by Bay K 8644 in decreasing order were B-HT 958 greater than B-HT 920 greater than St 587 greater than PE. These results suggest that Bay K 8644 preferentially improves the receptor-response coupling of alpha-adrenoceptor agonists with low intrinsic activity (alpha 2-agonists) versus agonists with high intrinsic activity (alpha-agonists) in canine saphenous vein.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D007473:Ion Channels; C030655:St 587; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C024763:talipexole; C035813:B-HT 958; D003000:Clonidine