title: Effect of biliary cirrhosis on neurogenic relaxation of rat gastric fundus and anococcygeus muscle: role of nitric oxide pathway.
abstract: BACKGROUND
  Cirrhosis, associated with a host of hemodynamic abnormalities, could affect the gastrointestinal (GI) tract motility. On the other hand, the nonadrenergic noncholinergic (NANC) neurotransmission has been shown to play a pivotal role in GI tract motility and has been linked with release of nitric oxide (NO) on electrical stimulation. In this study, we investigated the effect of biliary cirrhosis on the neurogenic relaxation of rat gastric fundus and anococcygeus muscle and also the possible role of nitric oxide system in this manner.
  
  
  METHODS
  Isolated gastric fundus and anococcygeus strips of sham-operated and biliary cirrhotic (4 weeks after bile duct ligation) rats were mounted under tension in a standard organ bath. Electrical stimulation was applied to obtain NANC-mediated relaxations in precontracted gastric fundus and anococcygeus muscle. The neurogenic relaxations were examined in the presence of different doses of NO synthase inhibitor, N (w)-Nitro-L-Arginine Methyl Ester (L-NAME). The concentration-dependent relaxant responses to the NO donor sodium nitroprusside were also evaluated.
  
  
  RESULTS
  The neurogenic relaxation of both gastric fundus and anococcygeus muscle was significantly (P < 0.001) increased in cirrhotic animals. L-NAME (0.03-1,000 µM) inhibited relaxations in both groups in a dose-dependent manner (P < 0.001), but cirrhotic groups were more resistant to the inhibitory effects of L-NAME (P < 0.01). Sodium nitroprusside-mediated relaxations were similar in two groups.
  
  
  CONCLUSIONS
  This study for the first time demonstrated that cirrhosis increases the NO-mediated neurogenic relaxation of both rat gastric fundus and anococcygeus muscle, suggesting a crucial role for the neurogenic NO in the pathophysiology of disturbed GI motility in cirrhosis.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghasemi
authors.forename: Ali Reza
authors.initials: AR
authors.lastname: Karimollah
authors.forename: Bardia
authors.initials: B
authors.lastname: Bakhtiari
authors.forename: Abbas
authors.initials: A
authors.lastname: Ghasemi
authors.forename: Leila
authors.initials: L
authors.lastname: Moezi
authors.forename: Arash
authors.initials: A
authors.lastname: Bahremand
authors.forename: Pouya
authors.initials: P
authors.lastname: Ziaei
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008105:Liver Cirrhosis, Biliary; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000294:innervation* / Q000502:physiology
chemical_list: D009599:Nitroprusside; D019331:NG-Nitroarginine Methyl Ester