Letter To The Editors

Effect of the topical application of nitroglycerin on intraocular pressure in normal and glaucomatous monkeys

The effects of various nitric oxide compounds and their inhibitors on monkey ciliary muscle contraction in vitro were investigated in both the longitudinal and circular vectors. The responses to nitric oxide compounds in carbachol precontracted ciliary muscle consisted of an initial relaxation often followed by recovery to near carbachol precontracted levels while the compound was still present. Sodium nitroprusside produced the greatest relaxation responses (nearly 100% relaxation in both vectors at 10⁻³ M). The highest concentrations of isosorbide dinitrate (10⁻⁴ M) and l-arginine (10⁻³ M) produced relaxation responses of approximately 50% in both vectors. 8-Bromo cyclic GMP produced the smallest relaxation responses (25–35%). Nitric oxide synthase inhibition enhanced carbachol contraction up to 20% in the longitudinal but not the circular vector. Phosphodiesterase inhibition did not further enhance the relaxation response to l-arginine. Guanylate cyclase inhibition partially attenuated the relaxation response to sodium nitroprusside. Nitric oxide generating compounds were effective in relaxing precontracted monkey ciliary muscle in vitro. Endogenous production of nitric oxide is likely involved in the regulation of the contractile response in monkey ciliary muscle. Nitric oxide generating compounds may have potential value in therapeutic areas where modulation of ciliary muscle tension is desirable.

In the recent years it has been recognized that nitric oxide is an important regulator of ocular blood flow. Nitric oxide is involved in the control of basal blood flow in the choroid, optic nerve and the retina. In addition, nitric oxide mediates a number of vasodilator responses in ocular vessels to agonists such as acetylcholine, bradykinin, histamine, substance P and insulin. Nitric oxide also plays a role in hypercapnia-induced vasodilation in the choroid and is a modulator of pressure autoregulation in this vascular bed. Abnormalities of the l-arginine/nitric oxide system have been observed in a variety of ocular diseases including glaucoma, diabetic retinopathy and retinopathy of prematurity. This makes the l-arginine/nitric oxide pathway an attractive target for therapeutic interventions. Additional research is required, particularly in characterizing the role of the three nitric oxide synthase isoforms in the control of ocular perfusion, to implement this concept into the clinical management of ocular diseases.

Nitric oxide generated by three distinct enzyme systems appears to play a critical role in many diverse physiological processes. Using both conventional and immunohistochemical techniques, nitric oxide synthases have been identified throughout the body, including all regions of the eye. A large number of in vitro and in vivo preparations have been utilized showing nitric oxide to have an important role in regulation of regional ocular blood flow. Nitric oxide-mediated control of basal ocular blood flow is demonstrated by vasoconstriction seen in experiments where vascular endothelial cells are removed, or when nitric oxide synthase is inhibited. The endogenous source of nitric oxide in the eye appears to be both endothelial and neural. In addition, administration of drugs that can `donate' nitric oxide produces vasodilation of the eye vasculature. Local vasodilation in response to illumination of the retina is controlled by generation and release of nitric oxide, whereas most other physiological adjustments of ocular blood flow (i.e., autoregulation and responses to altered blood gas levels) seem to be relatively independent of nitric oxide mechanisms. Nitric oxide is implicated in a variety of ocular pathophysiological states including uveitis, retinal ischemic disease, diabetes and glaucoma.