Different responsiveness to nitric oxide-cyclic guanosine monophosphate pathway in cholinergic and tachykinergic contractions of the rabbit iris sphincter muscle.
OBJECTIVE
In the rabbit iris sphincter muscle, sodium nitroprusside (SNP), a nitric oxide (NO) donor, inhibits cholinergic contraction but does not affect tachykinergic contraction in vitro. The objectives of the current study were to clarify the mechanism for the different responsiveness to NO in cholinergic and tachykinergic muscular contractions, and to examine whether the mechanism for NO-induced inhibition of cholinergic muscular contraction is operative in vivo.


METHODS
Iris sphincter muscle was dissected from the rabbit eye pretreated with or without endotoxin (lipopolysaccharide, LPS) in vivo. Cyclic guanosine monophosphate (cGMP) content in the iris sphincter muscle was determined by radioimmunoassay. The motor activity of the ring-shaped iris sphincter muscle was measured isometrically. Sodium nitroprusside, carboxy-2-phenyl-4,4,5,5,-tetramethyl-imidazoline-1-oxyl-3-oxide (C-PTIO, a scavenger of NO radicals), and 8-bromo cGMP (a permeable cGMP analogue) were administered between the first and second administrations of carbachol and neurokinin A, both of which had caused sustained contraction in the iris sphincter 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 significantly reduced SNP-induced cGMP accumulation in the muscle, as well as the SNP-induced inhibition of muscular contraction caused by carbachol. Neither carbachol nor neurokinin A influenced SNP-induced cGMP accumulation in the muscle. Induction of 8-bromo-cGMP significantly diminished the muscular contraction caused by carbachol but not that caused by neurokinin A. In vivo pretreatment of the eye with LPS increased, in a time-dependent manner, the cGMP accumulation in the iris sphincter muscle, which was significantly inhibited by pretreatment of NG-nitro-L-arginine methyl ester (an inhibitor of NO synthesis) in vivo.


CONCLUSIONS
These results demonstrate that in rabbits the increase in cGMP accumulation induced by NO in the iris sphincter muscle is involved in the cholinergic contraction but not in the tachykinergic contraction, suggesting that different sensitivities to cGMP are essential for the different responsiveness to NO. Furthermore, the results of this study showed that the NO-cGMP pathway is operative in vivo and regulates iris sphincter muscle tone, at least when the eyes are infected with bacteria.
Chuman
H
H
Department of Ophthalmology, Miyazaki Medical College, Japan.
Chuman
T
T
Nao-i
N
N
Sawada
A
A
Yamamoto
R
R
Kobayashi
H
H
Wada
A
A
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007498:Iris / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D015288:Neurokinin A / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D011863:Radioimmunoassay
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D007093:Imidazoles; D018721:Muscarinic Agonists; D009599:Nitroprusside; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D015288:Neurokinin A; D002217:Carbachol; D006152:Cyclic GMP