NITRIC-OXIDE RELAXES BOVINE CILIARY MUSCLE CONTRACTED BY CARBACHOL THROUGH ELEVATION OF CYCLIC-GMP

It is generally accepted that nitric oxide relaxes vascular smooth mus cles by activating guanylyl cyclase, which in turn increases cyclic 3' :5' guanosine monophosphate level. Despite the physiological significa nce of nitric oxide, very few studies have attempted to characterize t he mode of action of this mediator in ciliary muscles. Therefore, the present experiments were designed to investigate whether or not the re laxation induced by sodium nitroprusside as a donor of nitric oxide is accompanied by the increase in cyclic 3': 5' guanosine monophosphate level in the bovine ciliary muscle, and these responses are affected b y methylene blue as an inhibitor of guanylyl cyclase and 3-isobutyl-1- methylxanthine as an inhibitor of phosphodiesterases. The relaxation a ctivity of exogenous 8-bromo-cyclic 3':5' guanosine monophosphate was also determined. Sodium nitroprusside produced a concentration-depende nt relaxation in the bovine ciliary muscle strips which had been contr acted by carbachol as a cholinergic agonist. Relaxation in response to sodium nitroprusside was accompanied by a significant (P < 0.05 and P < 0.005) increase in cyclic 3':5' guanosine monophosphate level. The relaxation response and the increase in cyclic 3':5' guanosine monopho sphate caused by sodium nitroprusside were significantly (P < 0.01 and P < 0.05) augmented by the pretreatment with 3-isobutyl-1-methylxanth ine, and were significantly (P < 0.005 and P < 0.05) attenuated in the presence of methylene blue. The exogenously applied 8-bromo-cyclic 3' :5' guanosine monophosphate relaxed the ciliary muscle strips in a con centration-dependent manner. These results suggest that nitric oxide c auses relaxation of the bovine ciliary muscle through the activation o f guanylyl cyclase and an increase in cyclic 3':5' guanosine monophosp hate level. (C) 1998 Academic Press Limited.