Vasorelaxant Effects of Racemic Betaxolol and its R- and S- Isomers on Bovine Retinal Vessels

PURPOSE: RS-Betaxolol (equimolar R- and S- isomers) lowers intraocular pressure and dilates precontracted retinal and posterior ciliary arteries in vitro. Betaxolol's vasorelaxant effect is thought to involve the inhibition of calcium influx into vascular smooth muscle and is unrelated to its stereoselective beta-adrenergic blocking action. The authors assessed the vasodilatory effect of RS-betaxolol on different diameters of bovine retinal arterioles and venules, and these responses were compared with the responses induced by R- and S-betaxolol isomers in vitro. METHOD: In-vitro preparations of the bovine retinal microcirculatory system were perfused continuously with oxygenated, heparinized physiological salt solution at 37 degrees C. Diameters of retinal arterioles and venules were measured using video imaging. The retinal vessels were preconstricted with 40 mM KCl, and concentration-response curves for vasodilation were obtained for RS-betaxolol, R-betaxolol, and S-betaxolol. RESULTS: Baseline diameters of first-order (A1) and second-order (A2) branches of retinal arterioles were 50 +/- 0.6 microm and 39 +/- 1 microm, respectively (n = 20), whereas diameters of first-order (V1) and second-order (V2) branches of venules were 75 +/- 0.8 microm and 50 +/- 0.4 mM, respectively (n = 20). The diameters of all sizes of retinal arterioles and venules were significantly reduced (i.e., vasoconstricted) in the presence of 40 mM KCl (n = 20). These preconstricted vessels were relaxed in a dose-dependent manner by cumulative additions of RS-betaxolol, R-betaxolol, and S-betaxolol. The dose-response curves of these compounds were not significantly different. CONCLUSION: RS-Betaxolol, R-betaxolol, and S-betaxolol were equiactive and produced concentration-dependent vasodilatation of all sizes of retinal arterioles and venules studied.