OCULAR HYPOTENSIVE AND VASODILATIVE EFFECTS OF 2 BETA-ADRENERGIC BLOCKERS WITH INTRINSIC SYMPATHOMIMETIC ACTIVITY

Purpose. The ocular hypotensive and vasodilative effects of vaninolol and eugenolol, two beta-adrenergic blockers with intrinsic sympathomim etic activity, were tested in rabbits and their pharmacologic mechanis ms were also studied in vitro. Methods. Intraocular pressure was measu red in ocular hypertonic rabbits which were induced by infusing 20% Na Cl or 5% glucose solution. The rabbit's ocular blood flow was determin ed using the colored microsphere technique. The concentrations of cAMP were evaluated in porcine ciliary body and cultured A7r5 smooth muscl e cells by radioimmunoassay. Ca+2 concentration was measured in A7r5 c ells by spectrofluorometry after loading cells with Fura-2-AM. Results . It was found that 0.5% eugenolol and vaninolol could suppress the in traocular pressure in glucose-induced ocular hypertensive rabbits and delay the intraocular pressure recovery in NaCl-induced ocular hyperte nsive rabbits. In addition, both agents improved the ocular blood flow in the iris, ciliary body, retina and choroid. Vaninolol and eugenolo l of 10 mu M inhibited the basal cAMP accumulation from 23.9 +/- 2.0 o f control to 8.7 +/- 0.4 and 2.4 +/- 0.1 respectively and inhibited th e 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. Th e cellular cAMP concentration was significantly increased from 10 +/- 1 of control to 96 +/- 5 (vaninolol) and 38 +/- 3 (eugenolol) in cultu red A7r5 smooth muscle cells. Both agents also increased the intracell ular calcium concentration in A7r5 cells. Conclusions. These results i ndicate that the lowering of intraocular pressure by vaninolol and eug enolol may be due to cAMP suppression in the ciliary body by beta-anta gonist and/or alpha 2-agonist activities. Both agents cause vasodilati on via beta 2-agonist action that increase the smooth muscle cellular cAMP level more than vasoconstriction via cr-agonist activity by incre asing an influx of extracellular Ca+2.