Demonstration of beta 1-adrenoceptor mediating relaxation of porcine coronary artery by radioligand binding and pharmacological methods.

beta-adrenoceptors in the porcine coronary artery were characterized by a radioligand binding assay using (-)-[3H]dihydroalprenolol (DHA) and also by measuring the relaxant response of isolated coronary artery to norepinephrine. Specific (-)-[3H]DHA binding in the porcine coronary artery was saturable, reversible and of high affinity (Kd = 1.6 nM) with a maximal number of binding sites of 63 fmol/mg protein, and it showed a pharmacological specificity as well as stereoselectivity which characterized beta-adrenoceptors. The Hofstee analysis of inhibition of (-)-[3H]DHA binding by atenolol, practolol and ICI 118551 has shown that the averaged concentration of beta 1 and beta 2-adrenoceptors in this tissue was 68% and 32% respectively. The relaxant response of isolated coronary artery to norepinephrine was competitively antagonized by (-)propranolol, (+)propranolol, atenolol, practolol and ICI 118551. The pA2 values of these adrenoceptor antagonists were significantly correlated with the Ki values for beta 1 but not beta 2-adrenoceptors determined by the (-)-[3H]DHA binding assay. Thus, the present study demonstrates that the relaxant response of porcine coronary artery to norepinephrine is predominantly mediated through the stimulation of beta 1-adrenoceptors on vascular smooth muscles.