Effects of topical beta-blockers on the diameter of the isolated porcine short posterior ciliary artery.

PURPOSE Based on diameter measurements on the short posterior ciliary artery, this study was intended to determine the direct pharmacologic effect of beta-blockers; to determine the differences among a selective beta-blocker betaxolol, a beta-blocker with intrinsic sympathetic activity befunolol, and a nonselective beta-blocker timolol; and to find experimental evidence for the indirect hemodynamic effect of beta-blockers. METHODS A segment of isolated porcine short posterior ciliary artery was cannulated at both ends and mounted in a pressurized vessel chamber. Vessel diameter was measured as a function of beta-blocker concentration and as a function of change in transmural pressure. RESULTS In the absence of flow, the mean effective doses (ED50) were 0.8 +/- 0.3 mM, 1.0 +/- 0.3 mM, and 11.6 +/- 6.6 mM (SEM) for betaxolol, befunolol, and timolol, respectively. In the presence of flow, vessel diameter increased with an increase of transmural pressure. The mean relative diameter increased 4.2% +/- 1.0% (SEM) at a transmural pressure step from 30 mm Hg to 60 mm Hg. This increase was not significantly dependent on the presence of any of the beta-blockers. CONCLUSIONS Only at concentrations far exceeding their expected plasma concentrations, betaxolol, befunolol, and timolol increased the diameter of the isolated porcine short posterior ciliary artery, as a result of their direct pharmacologic effect. Only the difference between the vasodilatory potency of the selective and the nonselective beta-blocker was significant: ED50 of betaxolol was 15 times smaller than ED50 of timolol. There was a positive correlation between the diameter of the isolated porcine short posterior artery (when used as a model for an intraocular artery) and the transmural pressure, which corroborates the indirect hemodynamic effect of beta-blockers. It is speculated that instillation of topical beta-blockers into the conjunctival sac may increase the perfusion of the optic nerve head by an indirect hemodynamic mechanism, but not by a direct pharmacologic mechanism.