DIFFERENT RESPONSIVENESS TO NITRIC-OXIDE CYCLIC GUANOSINE-MONOPHOSPHATE PATHWAY IN CHOLINERGIC AND TACHYKINERGIC CONTRACTIONS OF THE RABBITIRIS SPHINCTER MUSCLE

Purpose. In the rabbit iris sphincter muscle, sodium nitroprusside (SN P), a nitric oxide (NO) donor, inhibits cholinergic contraction but do es not affect tachykinergic contraction in vitro. The objectives of th e current study were to clarify the mechanism for the different respon siveness to NO in cholinergic and tachykinergic muscular contractions, and to examine whether the mechanism for NO-induced inhibition of cho linergic muscular contraction is operative in vivo. Methods. Iris sphi ncter muscle was dissected from the rabbit eye pretreated with or with out endotoxin (lipopolysaccharide, LPS) in vivo. Cyclic guanosine mono phosphate (cGMP) content in the iris sphincter muscle aas determined b y radioimmunoassay. The motor activity of the ring-shaped iris sphinct er muscle was measured isometrically. Sodium nitroprusside, yl-4,4,5,5 ,-tetramethyl-imidazoline-1-oxyl-3-oxide (C-PTIO, a scavenger of NO ra dicals), and 8-bromo cGMP (a permeable cGMP analogue) were administere d between the first and second administrations of carbachol and neurok inin A, both of which had caused sustained contraction in the iris sph incter muscle. Results. Sodium nitroprusside inhibited the contraction of the iris sphincter muscle caused by carbachol but had no effect on the contraction caused by neurokinin A. Application of C-PTIO signifi cantly reduced SNP-induced cGMP accumulation in the muscle, as well as the SNP-induced inhibition of muscular contraction caused by carbacho l. Neither carbachol nor neurokinin A influenced SNP-induced cGMP accu mulation in the muscle. Induction of 8-bromo-cGMP significantly dimini shed the muscular contraction caused by carbachol but not that caused by neurokinin A. In vivo pretreatment of the eye with LPS increased, i n a time-dependent manner, the cGMP accumulation in the iris sphincter muscle, which was significantly inhibited by pretreatment of N-G-nitr o-L-arginine methyl ester (an inhibitor of NO synthesis) in vivo. Conc lusions. These results demonstrate that in rabbits the increase in cGM P accumulation induced by NO in the iris sphincter muscle is involved in the cholinergic contraction but not in the tachykinergic contractio n, suggesting that different sensitivities to cGMP IP are essential fo r the different responsiveness to NO. Furthermore, the results of this study showed that the NO-cGMP pathway is operative in vivo and regula tes iris sphincter muscle tone, at least when the eyes are infected wi th bacteria.