Portal hypertension activates the nitric oxide synthase genes in the esophageal mucosa of rats

Background & Aims: Nitric oxide is associated with hyperdynamic circulation and development of collaterals in portal hypertension. The aim of this study was to investigate whether NO synthase is activated in the portal-hypertensive esophagus. Methods: In esophageal specimens after portal ligation or sham operation, the expression of constitutive and inducible NO synthase messenger RNA was assessed by reverse transcription-polymerase chain reactions. NO synthase protein at 14 postoperative days was visualized with immunofluorescence staining with specific antibodies against constitutive and inducible NO synthase. Results: The esophageal muscularis mucosae and epithelium overlying large submucosal veins in portal-hypertensive rats were significantly thinner than in controls (muscularis mucosae, 24.3% thinner, P < 0.01; epithelium, 23.0% thinner, P < 0.05). Expression of NO synthase proteins in endothelia of submucosal veins was significantly higher in portal-hypertensive rats than in controls (constitutive NO synthase, 17.6%; inducible NO synthase, 18.0% increased over controls, respectively; P < 0.01). Expression of both constitutive and inducible NO synthase messenger RNA in portal-hypertensive vats was significantly increased (constitutive NO synthase, 10-fold; inducible NO synthase, 20-fold at 14 days vs. controls; P < 0.01). Conclusions: Portal hypertension triggers overexpression of NO synthase messenger RNA and protein in the rat esophageal mucosa. This phenomenon, combined with the thinness of muscularis mucosae and epithelium, may facilitate development and rupture of esophageal varices.