Differential effects of calcium antagonists and Bay K 8644 on contractile responses to exogenous noradrenaline and adrenergic nerve stimulation in the rabbit ear artery.
1. The effects of three calcium antagonists (nifedipine, verapamil, diltiazem) and the calcium agonist Bay K 8644 were compared on contractile responses of similar amplitude elicited by noradrenaline (NA) and electrical nerve stimulation (ENS) in the rabbit isolated ear artery. 2. Contractions induced by both NA (3 x 10(-7) M) and ENS (10 Hz, 10s) were almost exclusively mediated by alpha 1-adrenoceptors, since 10(-7) M prazosin abolished (NA) or almost abolished (ENS) the responses, and prazosin was more than three orders of magnitude more potent than rauwolscine on both types of response. 3. ENS-induced contractions were considerably less inhibited by nifedipine, verapamil and diltiazem than were those elicited by NA. Bay K 8644 enhanced responses to NA more than those to ENS. 4. The inhibitory effect of nifedipine and Ca2+ deprivation on NA-induced contractions decreased with increasing NA concentration. Reduction of the NA response by prazosin or phenoxybenzamine increased the nifedipine inhibition. 5. Reduction of the ENS-induced contractions by prazosin or phenoxybenzamine, or by use of a lower stimulation frequency did not increase the inhibitory effect of nifedipine. 6. In conclusion, the differential effects of the calcium antagonists on NA- and ENS-induced contractions were not related to differences in alpha-adrenoceptor subtype (alpha 1/alpha 2), receptor reserve or response amplitude, but may rather reflect temporal and spatial differences in alpha-adrenoceptor activation between the responses.
Skärby
T V
TV
Department of Clinical Pharmacology, Lund University, Sweden.
Högestätt
E D
ED
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; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004431:Ear, External / Q000098:blood supply; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D013779:Tetrodotoxin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine