Effect of diltiazem upon contractile responses to phenylephrine, cirazoline, Sgd 101/75, St 587 and B-HT 920 in rabbit aorta and dog saphenous vein preparations.
Diltiazem (10 microM) did not significantly affect concentration-response curves to the full, relatively selective alpha 1-adrenoceptor agonists phenylephrine and cirazoline in rabbit aorta and dog saphenous vein preparations. The effects of these 2 agonists remained resistant to diltiazem even in tissues pretreated with phenoxybenzamine (0.03 or 0.1 microM, 20 min) to reduce the alpha-adrenoceptor reserve. Sgd 101/75 and St 587 were partial agonists in both vascular preparations. The concentration-response curves to these relatively selective alpha 1-adrenoceptor agonists were also unaffected, or only slightly attenuated, by diltiazem. B-HT 920 at low concentrations preferentially stimulated the dog saphenous vein preparation and only at high concentrations elicited small contractions of the rabbit aorta. The responses to B-HT 920 were mediated by alpha 2-adrenoceptors in the vein and by alpha 1-adrenoceptors in the aorta yet concentration-response curves to this agonist were significantly attenuated by diltiazem in both tissues. The results indicate that the resistance of certain alpha-adrenoceptor-mediated responses in vascular preparations to calcium entry blockers need not be associated with the presence of a significant receptor reserve and that calcium dependency of a response may be determined by the agonist.
Bou
J
J
Massingham
R
R
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001381:Azepines / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D012501:Saphenous Vein / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D001552:Benzazepines; D007093:Imidazoles; C030655:St 587; D010656:Phenylephrine; C024763:talipexole; D004110:Diltiazem; D003000:Clonidine; C034204:indanidine; C014282:cirazoline