Influence of Bay K 8644 on vascular responses mediated by alpha 1- and alpha 2-adrenoceptors.
1. The calcium channel activator Bay K 8644 increased the potency of noradrenaline in cat middle cerebral (alpha 2-adrenoceptors) and mesenteric (atypical or mixed alpha 1- and alpha 2-adrenoceptor population) arteries, but not in rat middle cerebral and mesenteric arteries (alpha 1-adrenoceptors). 2. In cat arteries, exposure to 15 mM K+ solution shifted the noradrenaline concentration-response curve to the left in an almost identical manner as did Bay K 8644. 3. Bay K 8644 completely reversed the relaxation produced by nifedipine in K+-contracted cat middle cerebral arteries, whereas the relaxation induced by verapamil, diltiazem or flunarizine was only partially reversed. This suggests a specific interaction between Bay K 8644 and the dihydropyridine receptors on the calcium channels. 4. It is concluded that the degree to which noradrenaline promotes calcium influx through membrane channels is at least partly related to the alpha-adrenoceptor subtype mediating the response.
Högestätt
E D
ED
Department of Clinical Pharmacology, University of Lund, Sweden.
Skärby
T V
TV
Uski
T K
TK
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D011942:Receptors, Adrenergic, alpha; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009638:Norepinephrine