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, theta=237 microm), 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 approximately 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 F2alpha (PGF2alpha)-induced force, which depended less on Ca2+ influx than did K+-induced force: K+-, but not PGF2alpha-induced contractions were abolished in Ca2+-free medium. The minor betaxolol-induced relaxation of tonic PGF2alpha-induced force was blocked in Ca2+-free medium. With repeated exposures to PGF2alpha in Ca2+-free medium, initial phasic PGF2alpha-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 PGF2alpha phasic force did not decline, indicating that phasic force primarily depended on Ca2+ released from intracellular stores. Both beta-blockers failed to relax phasic PGF2alpha-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.
Hoste
A M
AM
Department of Human Physiology and Pathophysiology, University of Antwerp, Belgium.
Sys
S U
SU
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D015784:Betaxolol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D012160:Retina / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D011433:Propranolol; D015237:Dinoprost; D014700:Verapamil; D015784:Betaxolol; D011188:Potassium; D002118:Calcium