Nitric oxide-sensitive and -insensitive contractions of the isolated rabbit iris sphincter muscle.
OBJECTIVE
The rabbit iris sphincter muscle is innervated by cholinergic and tachykinergic nerves that regulate its tone. To clarify the involvement of nitric oxide (NO) in the postsynaptic regulation of the rabbit iris sphincter muscle tone, the authors examined the effects of NO-related agents on the cholinergic contraction induced by carbamylcholine (carbachol) and the tachykinergic contraction induced by neurokinin A.


METHODS
The motor activity of the ring-shaped rabbit iris sphincter muscle was measured isometrically. Sodium nitroprusside (SNP, a NO donor) was administered between the first and second administrations of carbachol and neurokinin A, each of which induced sustained contraction. The effects of carboxy-2-phenyl-4,4,5,5,-tetramethyl-imidazoline-l-oxyl-3-oxide (carboxy-PTIO, a scavenger of NO radicals), NG-monomethyl-L-arginine (L-NAME, an inhibitor of NO formation from L-arginine), and methylene blue (an inhibitor of soluble guanylate cyclase) on contractions induced by carbachol and neurokinin A also were studied. Cyclic guanosine monophosphate (GMP) content in the muscle was determined by radioimmunoassay.


RESULTS
Sodium nitroprusside inhibited carbachol-induced contractions of the iris sphincter muscle in a concentration-dependent manner but had no effect on neurokinin A-induced muscle contractions. Carboxy-PTIO and methylene blue significantly diminished the inhibitory effect of SNP on carbachol-induced contractions. L-NAME had no effect on contractions induced by either carbachol or neurokinin A. Sodium nitroprusside alone increased cyclic GMP accumulation in a concentration-dependent manner.


CONCLUSIONS
This study showed that SNP inhibited cholinergic contractions mainly through a cyclic GMP-dependent mechanism but did not affect the tachykinergic contractions, indicating that cholinergic contraction is NO sensitive, whereas tachykinergic contraction is NO insensitive. These findings suggest that in rabbits, the cholinergic and tachykinergic responses have distinct features for the fine adjustment of the iris sphincter muscle tone.
Chuman
T
T
Department of Ophthalmology, Miyazaki Medical College, Japan.
Chuman
H
H
Nao-i
N
N
Sawada
A
A
Yamamoto
R
R
Wada
A
A
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007093:Imidazoles / Q000494:pharmacology; D007498:Iris / Q000502:physiology*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D008916:Miotics / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D015288:Neurokinin A / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D011680:Pupil / Q000502:physiology; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000378:metabolism
D001565:Benzoates; D004791:Enzyme Inhibitors; D007093:Imidazoles; D008916:Miotics; D011950:Receptors, Cholinergic; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009599:Nitroprusside; D009569:Nitric Oxide; D015288:Neurokinin A; D002217:Carbachol; D001120:Arginine; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester