Hepatology International

, Volume 7, Issue 2, pp 622–635

Nitric oxide and prostaglandin as mediators in the pathogenesis of hyperkinetic circulatory state in a model of endotoxemia-induced portal hypertension

  • Moattar Raza Rizvi
  • Mohammad Tauseef
  • Mohd Shahid
  • Rashmi Babbar
  • Mohammad Fahim
  • Puja Sakhuja
  • Shiv Kumar Sarin
Original Article

DOI: 10.1007/s12072-012-9397-9

Cite this article as:
Rizvi, M.R., Tauseef, M., Shahid, M. et al. Hepatol Int (2013) 7: 622. doi:10.1007/s12072-012-9397-9
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Abstract

Aims

To evaluate the participation of nitric oxide (NO) and prostaglandin (PGI2) on hyperdynamic state in endotoxemia-induced portal hypertension (EIP) induced by chronic endotoxemia.

Methods

The portal pressure (PP) and mean arterial pressure (MAP) were recorded, in vivo before and after administration of l-NAME (NOS inhibitor) and indomethacin (specific blocker of COX). The vasoactive responses to acetylcholine of thoracic rat aortic rings were studied in vitro before and after nitric oxide and cyclooxygenase blockade using multichannel organ bath. The mRNA expression for isoforms of (cyclooxygenase) COX and nitric oxide synthase (NOS) were analyzed using RT-PCR.

Results

Administration of both l-NAME and indomethacin in EIP rabbits significantly reduced (p < 0.05) the PP and reversed the MAP to normal as compared to sham-operated (SO) rabbits. There was impaired vasodilatory response to acetylcholine in EIP rabbits. l-NAME caused a significant reduction in acetylcholine-induced vasorelaxation in SO rabbits than EIP due to preexisting hyperemia in EIP. Indomethacin partially restored vasoresponsiveness to acetylcholine in EIP group. The mRNA expression of eNOS (endothelial NOS) and COX-1 (constitutive COX) were significantly higher in SO than EIP rabbits. iNOS (inducible NOS) and COX-2 (inducible COX) mRNA expression was seen only in EIP rabbits.

Conclusions

A significant component of acetylcholine-mediated vasorelaxation in EIP model is modulated by eNOS. There was increased production of contractile prostaglandin in EIP rabbits. iNOS and COX-2 play an important role in the hemodynamic abnormalities of PHT. This novel model of PHT produced by chronic splanchnic endotoxemia in rabbit, mimics impaired vasodilation and vasoreactivity akin to other models of PHT.

Keywords

Nitric oxide Prostaglandins Non-cirrhotic portal hypertension Vascular reactivity Cirrhosis 

Copyright information

© Asian Pacific Association for the Study of the Liver 2012

Authors and Affiliations

  • Moattar Raza Rizvi
    • 1
    • 5
  • Mohammad Tauseef
    • 2
  • Mohd Shahid
    • 2
  • Rashmi Babbar
    • 3
  • Mohammad Fahim
    • 2
  • Puja Sakhuja
    • 4
  • Shiv Kumar Sarin
    • 1
  1. 1.Department of GastroenterologyG. B. Pant HospitalNew DelhiIndia
  2. 2.Department of Physiology, V. Patel Chest InstituteUniversity of DelhiDelhiIndia
  3. 3.Department of PhysiologyMaulana Azad Medical CollegeDelhiIndia
  4. 4.Department of PathologyG. B. Pant HospitalNew DelhiIndia
  5. 5.College of Applied Medical ScienceAl-Majma’ah UniversityMajma’ahKingdom of Saudi Arabia

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