Nitric oxide relaxes bovine ciliary muscle contracted by carbachol through elevation of cyclic GMP.
It is generally accepted that nitric oxide relaxes vascular smooth muscles by activating guanylyl cyclase, which in turn increases cyclic 3':5' guanosine monophosphate level. Despite the physiological significance of nitric oxide, very few studies have attempted to characterize the mode of action of this mediator in ciliary muscles. Therefore, the present experiments were designed to investigate whether or not the relaxation 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 by methylene blue as an inhibitor of guanylyl cyclase and 3-isobutyl-1-methylxanthine as an inhibitor of phosphodiesterases. The relaxation activity of exogenous 8-bromo-cyclic 3':5' guanosine monophosphate was also determined. Sodium nitroprusside produced a concentration-dependent relaxation in the bovine ciliary muscle strips which had been contracted 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 monophosphate caused by sodium nitroprusside were significantly (P<0.01 and P<0.05) augmented by the pretreatment with 3-isobutyl-1-methylxanthine, 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 concentration-dependent manner. These results suggest that nitric oxide causes relaxation of the bovine ciliary muscle through the activation of guanylyl cyclase and an increase in cyclic 3':5' guanosine monophosphate level.
Kamikawatoko
S
S
Department of Ophthalmology, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113, Japan.
Tokoro
T
T
Ishida
A
A
Masuda
H
H
Hamasaki
H
H
Sato
J
J
Azuma
H
H
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002417:Cattle; D002924:Ciliary Body / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D007202:Indicators and Reagents / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D008916:Miotics / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology
D004338:Drug Combinations; D007202:Indicators and Reagents; D008916:Miotics; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; D002217:Carbachol; D000242:Cyclic AMP; D008751:Methylene Blue; D015056:1-Methyl-3-isobutylxanthine