title: The nonadrenergic noncholinergic relaxation of anococcygeus muscles of bile duct-ligated rats.
abstract: Previous studies have shown the naloxone-induced withdrawal syndrome and the development of tolerance in the tissues of cholestatic animals. Increased neuronal nitric oxide synthase (nNOS) expression is reported to exist in morphine-tolerant animals. This, together with evidence for nitric oxide (NO) overproduction in cholestasis, suggested the possibility of an alteration of nonadrenergic noncholinergic (NANC) relaxation of anococcygeus muscles of cholestatic rats. To study this, we used three main groups of animals: unoperated, sham-operated and bile duct-ligated. Electrical field stimulation, in the presence of atropine and guanethidine, caused NANC relaxation in the anococcygeus muscle which was enhanced in bile duct-ligated animals. N(G)-nitro-L-arginine methyl ester (L-NAME), a NOS blocker, caused a dose-dependent inhibition of the NANC relaxation. The IC(50)'s of L-NAME in 7-day (7.30+/-0.87 microM), 14-day (6.98+/-0.70 microM) and 21-day (8.25+/-1.40 microM) bile duct-ligated groups were significantly different from those of unoperated (1.69+/-0.30 microM) and sham-operated groups (1.90+/-0.27 microM). L-NAME (100 microM) completely inhibited the NANC relaxation response, suggesting that NANC relaxation in the rat anococcygeus muscle is mediated mainly via NO. The contraction response of the intact muscle to phenylephrine, an alpha(1)-adrenoceptor agonist, and the relaxation response of the phenylephrine-contracted muscle to sodium nitroprusside, an NO donor, were not different in unoperated, sham-operated and 7-day bile duct-ligated groups. These results showed that the smooth muscle component of NANC relaxation is not altered in anococcygeus muscles of bile duct-ligated rats. It can thus be concluded that the NANC relaxation in the anococcygeus of cholestatic rats is more resistant to a NOS blocker, providing evidence for increased nitrergic neurotransmission in the anococcygeus muscles of cholestatic rats.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. Dehpour@medscape.com
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Dehpour
authors.forename: Arash
authors.initials: A
authors.lastname: Seyyedi
authors.forename: Hossein
authors.initials: H
authors.lastname: Rastegar
authors.forename: Khodadad
authors.initials: K
authors.lastname: Namiranian
authors.forename: Leila
authors.initials: L
authors.lastname: Moezi
authors.forename: Hamed
authors.initials: H
authors.lastname: Sadeghipour
authors.forename: Mehdi
authors.initials: M
authors.lastname: Dehghani
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Jorjani
authors.forename: Farshad
authors.initials: F
authors.lastname: Roushanzamir
authors.forename: Abolhasan
authors.initials: A
authors.lastname: Ahmadiani
mesh_terms: D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001652:Bile Ducts / Q000187:drug effects / Q000502:physiology*; D002779:Cholestasis / Q000378:metabolism / Q000503:physiopathology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008026:Ligation; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase