ANTERIOR SEGMENT PHYSIOLOGY AFTER BUMETANIDE INHIBITION OF NA-K-CL COTRANSPORT

Purpose. To determine the effect of bumetanide inhibition of Na-K-Cl c otransport on aqueous humor formation and outflow facility in living c ynomolgus monkeys, outflow facility in organ-cultured human eyes, and contraction in bovine ciliary muscle and trabecular meshwork strips, i n vitro. Methods. Aqueous humor formation in monkeys was measured fluo rophotometrically for 6 hours, 1 to 6 weeks before, immediately after, and 2 to 6 weeks after bumetanide was adminis tered intravitreally (f inal concentration similar to 100 or 500 mu M) or intravenously (0.01 or 0.03 mg/ kg at 0 and 3 hours). Outflow facility in monkeys was dete rmined by two-level, constant-pressure perfusion of the anterior chamb er for 45 to 60 minutes before and after bumetanide was administered b y bolus intracameral injection (100 mu M, initial anterior chamber con centra tion) or by exchanging the anterior chamber with 2 ml 10, 100, or 500 mu M bumetanide. Urine volume was measured 3 hours after admini stration of intravenous bumetanide in various diluents. The effect on intraocular pressure in organ-cultured human eyes was determined for 4 8 hours by constant-flow-variable-pressure perfusion with 10 mu M bume tanide. Contraction of fresh bovine ciliary muscle and trabecular mesh work was measured isometrically with a force- length transducer system after exposure to 100 mu M bumetanide +/- 1 mu M carbachol, Results, The bumetanide concentrations used had little effect on outflow facili ty or on aqueous humor formation in normal monkeys, on intraocular pre ssure in organ-cultured human eyes, or on contraction of bovine ciliar y muscle and trabecular meshwork strips. Intravenous bumetanide increa sed urine volume, regardless of the diluent used. Conclusions, These r esults suggest that Na-K-Cl cotransport is not involved functionally i n regulation of aqueous humor inflow and outflow and in contractility of ciliary muscle and trabecular meshwork.