ALPHA-1 ADRENOCEPTORS AND CALCIUM IN ISOLATED CANINE CORONARY-ARTERIES

Abstract

Experiments were designed to define the postjunctional .alpha. adrenoceptor subtype(s) in large canine coronary arteries and to determine the dependency of contractions due to their activation upon the entry of extracellular Ca2+. Rings of left circumflex coronary artery were mounted at their optimal length for isometric tension recording in organ chambers filled with physiological salt solution. Phenylephrine and cirazoline were full agaonists relative to norepinephrine. Methoxamine was a partial agonist relative to norepinephrine whereas clonidine, xylazine, B-HT 920 [2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo [5,4c] azepine dihydrochloride] and B-HT 933 [6-ethyl-5,6,7,8-tetrahydro-4H-oxazolo [4,5-d]azepin-2-amine dihydrochloride] produced minimal contractions. Prazosin competitively inhibited the contractile response to phenylephrine (pA2 [competitive antagonistic activity] = 8.6), whereas rauwolscine caused a noncompetitive inhibition and was more than 100 times less potent than prazosin at inhibiting the response to phenylephrine. Similar results were obtained using norepinephrine (in the presence of propranolol) as the agonist. The Ca+2+ entry blockers nimodipine, verapamil and diltiazem inhibited contractions caused by norepinephrine phenylephrine and cirazoline. Removal of extracellular Ca2+ abolished the response to cirazoline. Evidently in large canine coronary arteries only .alpha.-1 adrenoceptors are present postjunctionally and responses due to .alpha.-1 adrenoceptor activation are dependent upon extracellular Ca2+.