Ocular hypotensive and vasodilative effects of two β-adrenergic blockers with intrinsic sympathomimetic activity

Abstract

Purpose. The ocular hypotensive and vasodilative effects of vaninolol and eugenolol, two β-adrenergic blockers with intrinsic sympathomimetic activity, were tested in rabbits and their pharmacologic mechanisms were also studied in vitro.Methods. Intraocular pressure was measured in ocular hyper-tonic rabbits which were induced by infusing 20% NaCl or 5% glucose solution. The rabbit's ocular blood flow was determined using the colored microsphere technique. The concentrations of cAMP were evaluated in porcine ciliary body and cultured A7r5 smooth muscle cells by radioimmunoassay. Ca+2 concentration was measured in A7r5 cells by spectrofluorometry after loading cells with Fura-2-AM.Results. It was found that 0.5% eugenolol and vaninolol could suppress the intraocular pressure in glucose-induced ocular hypertensive rabbits and delay the intraocular pressure recovery in NaCl-induced ocular hypertensive rabbits. In addition, both agents improved the ocular blood flow in the iris, ciliary body, retina and choroid. Vaninolol and eugenolol of 10 μM inhibited the basal cAMP accumulation from 23.9 ± 2.0 of control to 8.7 ± 0.4 and 2.4 ± 0.1 respectively and inhibited the isoproterenol-induced cAMP accumulation from 154.3 ± 13.6 to 120.6 ± 8.3 and 74.2 ± 6.1 respectively in the porcine ciliary body. The cellular cAMP concentration was significantly increased from 10 ± 1 of control to 96 ± 5 (vaninolol) and 38 ± 3 (eugenolol) in cultured A7r5 smooth muscle cells. Both agents also increased the intracellular calcium concentration in A7r5 cells.Conclusions. These results indicate that the lowering of intraocular pressure by vaninolol and eugenolol may be due to cAMP suppression in the ciliary body by β-antagonist and/or α2-agonist activities. Both agents cause vasodilation via β2-agonist action that increase the smooth muscle cellular cAMP level more than vasoconstriction via α-agonist activity by increasing an influx of extracellular Ca+2. Curr. Eye Res. 17: 700–707, 1998.