Increased endothelial nitric oxide synthase activity in the hyperemic vessels of portal hypertensive rats

J Hepatol. 1996 Sep;25(3):370-8. doi: 10.1016/s0168-8278(96)80124-3.


Background/aim: Portal hypertension is characterized by splanchnic hyperemia due to a reduction in mesenteric vascular resistance. Mediators of this hyperemia include nitric oxide. This is based on several reports indicating a marked splanchnic hyporesponsiveness in portal hypertension to vasoconstrictor stimuli both in vitro and in vivo, and a subsequent reversal using specific inhibitors of nitric oxide synthase. The objective of this study was to determine firstly whether the functional activity and/or expression of nitric oxide synthase is altered in portal hypertensive vasculature and secondly which isoenzyme form was responsible for the preferential response to nitric oxide blockade in these animals.

Methods: We compared nitric oxide synthase functional activity in the hyperemic vasculature of sham and portal hypertensive rats (following partial portal vein ligation). Nitric oxide synthase activities were determined by measuring the conversion of L-arginine to citrulline using ion-exchange chromatography and the amount of immunodetectable nitric oxide synthase in sham and portal hypertensive vessels was determined by Western blot.

Results: Ca(2+)-dependent nitric oxide synthase activity was significantly elevated (p < 0.05) in portal hypertensive particulate fractions from the superior mesenteric artery, thoracic aorta and portal vein. Vascular tissue cGMP levels and plasma nitrite levels were both significantly elevated in portal hypertension. Immunodetection with specific antisera raised against the inducible nitric oxide synthase demonstrated a lack of induction within the hyperemic vasculature. Immunodetection with antisera against endothelial nitric oxide synthase showed a significant increase in portal hypertensive portal vein only. These results demonstrate enhanced calcium-dependent nitric oxide synthase activity in portal hypertension hyperemic vessels concurrent with elevated tissue cGMP levels.

Conclusion: We conclude that enhanced endothelial nitric oxide synthesis may in part contribute to the hyperdynamic circulation of portal hypertension.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Cyclic GMP / metabolism
  • Endothelium, Vascular / enzymology*
  • Enzyme Induction
  • Humans
  • Hyperemia / enzymology*
  • Hypertension, Portal / enzymology*
  • Immune Sera
  • Ligation
  • Male
  • Mesenteric Arteries / metabolism
  • Nitric Oxide Synthase / metabolism*
  • Nitrites / blood
  • Portal Vein
  • Rats
  • Rats, Sprague-Dawley


  • Immune Sera
  • Nitrites
  • Nitric Oxide Synthase
  • Cyclic GMP