Nimodipine and inhibition of alpha adrenergic activation of the isolated canine saphenous vein.
The vascular smooth muscle of the canine saphenous vein contains both postjunctional alpha-1 and alpha-2 adrenoceptors. Experiments were designed to elucidate the relationship between alpha adrenoceptor subtypes and sensitivity to calcium entry blockade. Rings of canine saphenous vein were mounted at optimal length for isometric tension recording in organ chambers filled with physiological salt solution. Nimodipine inhibited potassium-induced contractions and depressed contractions to norepinephrine in the presence of prazosin, an alpha-1 adrenoceptor antagonist, but not under control conditions or in the presence of the alpha-2 adrenoceptor antagonist, rauwolscine. Nimodipine depressed the maximal response to B-HT 920, an alpha-2 adrenergic agonist and St-587, a partial alpha-1 adrenergic agonist, but did not affect that to cirazoline, a full alpha-1 adrenergic agonist. However, after treatment with phenoxybenzamine, nimodipine depressed the response to cirazoline. Nimodipine inhibited contractions to tyramine under control conditions or after prazosin but not after rauwolscine. Incubation in calcium-free solution depressed responses to St-587 and B-HT 920 more than those to cirazoline. Incubation in calcium-free solution plus ethylene glycol bis(beta-aminoethyl ether)-N,N-tetraacetic acid abolished responses to all alpha adrenergic agonists. These results suggest that the sensitivity to calcium entry blockade of alpha adrenergic responses is not determined by the subtype of alpha adrenoceptor. Rather, our findings support the concept that it is the efficacy of the agonist-receptor interaction or the efficiency of receptor-response coupling that determines the effect of calcium entry blockade on the adrenergic response.
Cooke
J P
JP
Rimele
T J
TJ
Flavahan
N A
NA
Vanhoutte
P M
PM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009539:Nicotinic Acids / Q000494:pharmacology*; D009553:Nimodipine; D011188:Potassium / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects; D014439:Tyramine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D002121:Calcium Channel Blockers; D009539:Nicotinic Acids; D011942:Receptors, Adrenergic, alpha; C030655:St 587; D009553:Nimodipine; C024763:talipexole; D003000:Clonidine; D011188:Potassium; D014439:Tyramine