Differential effects of calcium antagonists and Bay K 8644 on contractile responses to exogenous noradrenaline and adrenergic nerve stimulation in the rabbit ear artery

• Published in: British journal of pharmacology Vol. 101; no. 4; pp. 961 - 967
• Main Authors: Skärby, Tor V. Ch, Högestätt, Edward D.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.1990
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Animals; Arteries - drug effects; Calcium - physiology; Calcium Channel Blockers - pharmacology; Diltiazem - pharmacology; Ear, External - blood supply; Electric Stimulation; Female; In Vitro Techniques; Muscle Contraction - drug effects; Muscle, Smooth, Vascular - drug effects; Nifedipine - pharmacology; Norepinephrine - pharmacology; Rabbits; Sympathetic Nervous System - drug effects; Tetrodotoxin - pharmacology; Verapamil - pharmacology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1990.tb14188.x

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 × 10−7 m) and ENS (10 Hz, 10 s) were almost exclusively mediated by α1‐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 α‐adrenoceptor subtype (α1/α2), receptor reserve or response amplitude, but may rather reflect temporal and spatial differences in α‐adrenoceptor activation between the responses.