title: Nitric oxide and prostaglandin as mediators in the pathogenesis of hyperkinetic circulatory state in a model of endotoxemia-induced portal hypertension.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Gastroenterology, G. B. Pant Hospital, New Delhi, 110001, India. rajrizvi@yahoo.com.|College of Applied Medical Science, Al-Majma'ah University, Majma'ah, Riyadh, Kingdom of Saudi Arabia. rajrizvi@yahoo.com.
authors.forename: Moattar Raza
authors.initials: MR
authors.lastname: Rizvi
authors.affiliation: Department of Physiology, V. Patel Chest Institute, University of Delhi, Delhi, 110007, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Tauseef
authors.affiliation: Department of Physiology, V. Patel Chest Institute, University of Delhi, Delhi, 110007, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Shahid
authors.affiliation: Department of Physiology, Maulana Azad Medical College, Delhi, 110002, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Babbar
authors.affiliation: Department of Physiology, V. Patel Chest Institute, University of Delhi, Delhi, 110007, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Fahim
authors.affiliation: Department of Pathology, G. B. Pant Hospital, New Delhi, 110002, India.
authors.forename: Puja
authors.initials: P
authors.lastname: Sakhuja
authors.affiliation: Department of Gastroenterology, G. B. Pant Hospital, New Delhi, 110001, India.
authors.forename: Shiv Kumar
authors.initials: SK
authors.lastname: Sarin
keywords: Cirrhosis; Nitric oxide; Non-cirrhotic portal hypertension; Prostaglandins; Vascular reactivity