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Effect of Biliary Cirrhosis on Neurogenic Relaxation of Rat Gastric Fundus and Anococcygeus Muscle: Role of Nitric Oxide Pathway

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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.

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mehdi Ghasemi, Ali Reza Karimollah, Bardia Bakhtiari, Abbas Ghasemi, Arash Bahremand, Pouya Ziaei & Ahmad Reza Dehpour

  2. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Mehdi Ghasemi

  3. Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Leila Moezi

  4. Experimental Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Ahmad Reza Dehpour

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  1. Mehdi Ghasemi
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Correspondence to Ahmad Reza Dehpour.

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Ghasemi, M., Karimollah, A.R., Bakhtiari, B. et al. Effect of Biliary Cirrhosis on Neurogenic Relaxation of Rat Gastric Fundus and Anococcygeus Muscle: Role of Nitric Oxide Pathway. Dig Dis Sci 59, 2675–2681 (2014). https://doi.org/10.1007/s10620-014-3225-0

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