B-HT 920 acts as an ? 1-adrenoceptor agonist in the rabbit aorta under certain in vitro conditions

Abstract

Summary We have investigated the interaction of the α ₂-adrenoceptor agonist B-HT 920 with the α-adrenoceptors in the rabbit aorta using various experimental conditions. In standard Krebs-Henseleit solution B-HT 920 behaved as an antagonist when tested against the α ₁-agonist phenylephrine. However, it behaved as a partial agonist at α-receptors when subcontractile concentrations of various spasmogens (angiotensin II, serotonin, prostaglandin F_2α ) were applied, although no change in the affinity of the receptor to B-HT 920 was observed. By means of the selective antagonists prazosin and rauwolscine it was established that B-HT 920 activated α ₁-renoceptors. The same agonistic effects of B-HT 920 were obtained after pretreatment of the animal with reserpine or in the presence of ouabain. The various treatments used (except reserpine) did not influence the contractile response to phenylephrine. The contractile response to B-HT 920 was found to be highly susceptible to the calcium entry blocker nitrendipine whereas the response to phenylephrine was not. It is concluded that spasmogens modulate the responsiveness of α-receptors to certain agonists, possibly by causing a depolarization of the cell membrane and, thereby, sensitization of a mechanism involved in excitation-contraction coupling, conceivably a calcium gating mechanism.