RELAXATION OF TRABECULAR MESHWORK AND CILIARY MUSCLE BY RELEASE OF NITRIC-OXIDE

Purpose. Recent evidence suggests that nitric oxide (NO) is a major me ssenger molecule regulating smooth muscle contractility. A role for NO in aqueous humor dynamics, and thus regulation of intraocular pressur e, has been postulated. Recently, we described contractile properties of isolated bovine trabecular meshwork and ciliary muscle strips. To a ssess whether vasodilators contribute to the regulation of trabecular meshwork and ciliary muscle contractility, we measured the effect of v arious substances known to induce vasodilation by increasing intracell ular cGMP production. Methods. Measurements of isometric tension were performed on isolated bovine ciliary muscle and trabecular meshwork st rips using a custom-built electromagnetic force-length transducer. The effects of a membrane-permeable cGMP and an inhibitor of nitric oxide formation (L-nitroarginine L-NAG) were investigated. Organic nitrate (isosorbide dinitrate = ISDN, isosorbide-5-mononitrate = 5-ISMN) and n on-nitrate (sodium nitroprusside = SNP, S-nitroso-N-acetyl penicillami ne = SNAP) vasodilators were tested. Results. Isolated strips were pre contracted by carbachol 10(-6) mol/l for 30 minutes (100% carbachol ma ximal contraction). 8-bromo-cGMP 10(-4) mol/l evoked a relaxation to 8 6.7% +/- 1.4% (n = 8) in ciliary muscle and 58.6% +/- 5.4% (n = 7) in trabecular meshwork. Inhibition of NO-synthase by L-NAG increased the carbachol-induced contraction. The organic nitrovasodilators ISDN and 5-ISMN produced significant relaxations. The non-nitrates SNP and SNAP were the most potent relaxants. SNP 10(-4) mol/l relaxed the isolated ciliary muscle to 55.5% +/- 3.5% and the trabecular meshwork to 38.6% +/- 3.6%. ISDN and SNP were also tested on isolated strips without ca rbachol-induced precontraction. Both vasodilators had significant rela xing activity under these conditions. Conclusion. The data indicate th at an increase of intracellular cGMP by application of cGMP and organi c nitrate or non-nitrate vasodilators induces relaxation of the bovine trabecular meshwork and ciliary muscle. Thus, nitric oxide is a cotra nsmitter of smooth muscle relaxation in the chamber angle and may be i nvolved in the regulation of aqueous humor dynamics.