Ca2+ channel-blocking activity of propranolol and betaxolol in isolated bovine retinal microartery

The relaxant action of the standard beta-blocker propranolol was compared with betaxolol, a beta-blocker with established vasorelaxant properties. Ring segments of bovine retinal microartery (n = 36, ? = 237 um), which lacks adrenergic nerves and beta-adrenoceptors, were mounted in an organ bath for isometric force recording. l-, d-, dl-Propranolol and betaxolol were equally effective in relaxing tonic K+-induced contractions. The median effective dose (ED50) value was similar to 10(-5) M for both beta-blockers. The relaxation by both beta-blockers was unaffected by endothelium removal. Like verapamil, both beta-blockers induced smaller relaxation of tonic prostaglandin F-2 alpha (PGF(2 alpha))-induced force, which depended less on Ca2+ influx than did K+-induced force: K+-, but not PGF(2 alpha)-induced contractions were abolished in Ca2+-free medium. The minor betaxolol-induced relaxation of tonic PGF(2 alpha)-induced force was blocked in Ca2+-free medium. With repeated exposures to PGF(2 alpha) in Ca2+-free medium, initial phasic PGF(2 alpha)-induced force declined less with every exposure than did subsequent tonic force. When the preparations were briefly equilibrated with K+- and Ca2+-rich solution before every exposure to PGF(2 alpha), phasic force did not decline, indicating that phasic force primarily depended on Ca2+ released from intracellular stores. Both beta-blockers failed to relax phasic PGF(2 alpha)-induced force. Thus propranolol and betaxolol are equipotent vasorelaxant drugs in retinal microartery, both probably acting via Ca2+ channel blockade. This activity (that shows no stereospecificity) thus appears to be a more general property of beta-blockers. Microarteries might be more sensitive to this activity than are conductance arteries.