Relaxation of trabecular meshwork and ciliary muscle by release of nitric oxide.
OBJECTIVE
Recent evidence suggests that nitric oxide (NO) is a major messenger molecule regulating smooth muscle contractility. A role for NO in aqueous humor dynamics, and thus regulation of intraocular pressure, has been postulated. Recently, we described contractile properties of isolated bovine trabecular meshwork and ciliary muscle strips. To assess whether vasodilators contribute to the regulation of trabecular meshwork and ciliary muscle contractility, we measured the effect of various substances known to induce vasodilation by increasing intracellular cGMP production.


METHODS
Measurements of isometric tension were performed on isolated bovine ciliary muscle and trabecular meshwork strips 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 non-nitrate (sodium nitroprusside = SNP, S-nitroso-N-acetyl penicillamine = SNAP) vasodilators were tested.


RESULTS
Isolated strips were precontracted by carbachol 10(-6) mol/l for 30 minutes (100% carbachol maximal contraction). 8-bromo-cGMP 10(-4) mol/l evoked a relaxation to 86.7% +/- 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 carbachol-induced precontraction. Both vasodilators had significant relaxing activity under these conditions.


CONCLUSIONS
The data indicate that an increase of intracellular cGMP by application of cGMP and organic nitrate or non-nitrate vasodilators induces relaxation of the bovine trabecular meshwork and ciliary muscle. Thus, nitric oxide is a cotransmitter of smooth muscle relaxation in the chamber angle and may be involved in the regulation of aqueous humor dynamics.
Wiederholt
M
M
Institut für Klinische Physiologie, Klinikum Steglitz, Freie Universität Berlin, Germany.
Sturm
A
A
Lepple-Wienhues
A
A
D000594:Amino Acid Oxidoreductases / Q000502:physiology; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D002417:Cattle; D002924:Ciliary Body / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D007537:Isometric Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D014129:Trabecular Meshwork / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP