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M Avila, RW Seider, RA Stone, MM Civan; Inhibitors of NHE-1 Na+/H+ Exchange Reduce Mouse Intraocular Pressure . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4069.
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Purpose:To test if blocking the Na+/H+ antiport reduces intraocular pressure (IOP) in the mouse Methods:Using the electrophysiologic approach (the servo-null micropipette system) we previously adapted for continuously monitoring IOP in the mouse, we studied the effects of a series of transport inhibitors. Results:Topical application of 3 direct blockers of Na+/H+ exchangers produced comparable reductions in mouse IOP: Dimethylamiloride (DMA, -5.0±0.7 mmHg), ethylisopropylamiloride (EIPA, -4.1±1.0 mmHg) and BIIB723 (-4.9±1.7 mm Hg). These effects were mediated locally, not systemically, since adding DMA to one eye had no effect on the contralateral IOP. In contrast to the actions of selective inhibitors of Na+/H+ exchange, neither the low-potency inhibitor amiloride nor the inhibitor of Na+-K+-2Cl- cotransport bumetanide by itself was effective. Dorzolamide, which slows delivery of H+ and HCO3- to Na+/H+ and Cl-/HCO3- antiports, also reduced IOP by 2.9±0.6 mm Hg. After first blocking Na+/H+ exchange with DMA, EIPA, BIIB723 or dorzolamide, application of bumetanide produced an additional reduction in IOP of 3.8-4.0 mm Hg. Conclusion:The first step in aqueous humor formation is uptake of NaCl by the ciliary epithelial cells from the stroma, possibly by both paired Na+/H+ and Cl-/HCO3- antiports and a bumetanide-sensitive Na+-K+-2Cl- symport. The present data are consistent with electron probe X-ray microanalyses of rabbit ciliary epithelium indicating that the antiports are the dominant mechanism, and that bumetanide can produce a previously unobserved lowering of IOP when the Na+/H+ antiport is also inhibited
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