Portal hypertension triggers local activation of inducible nitric oxide synthase gene in colonic mucosa.

Recently a new clinical entity "portal hypertensive colopathy" has been reported. It involves vascular abnormalities and bleeding. Because nitric oxide may mediate these changes, we studied whether portal hypertension affects nitric oxide synthase in portal hypertensive colonic mucosa. In portal hypertensive and sham-operated rats the following studies were done: (1) colonic mucosal blood flow, (2) quantitative histologic examination, (3) reverse transcription-polymerase chain reaction for nitric oxide synthase mRNA, (4) nitric oxide synthase activity assay, and (5) immunostaining for nitric oxide synthase. In portal hypertensive rats, colonic mucosal blood flow and the number of submucosal veins were significantly increased in comparison to sham-operated rats. The mRNA expression and enzyme activity for inducible nitric oxide synthase (but not constitutive nitric oxide synthase) were significantly increased in portal hypertensive rats. Fluorescence signal intensity for inducible nitric oxide synthase in endothelia of mucosal and submucosal veins was significantly higher in portal hypertensive rats than in sham-operated rats. Portal hypertension activates inducible nitric oxide synthase gene and protein in colonic mucosal vessels. The excess of nitric oxide generated by overexpressed inducible nitric oxide synthase may play an important role in the development of vascular and hemodynamic abnormalities characterizing portal hypertensive colopathy.