Significance of Enhanced Expression of Nitric Oxide Syntheses in Splenic Sinus Lining Cells in Altered Portal Hemodynamics of Idiopathic Portal Hypertension

Idiopathic portal hypertension (IPH) is characterized by noncirrhotic portal hypertension due mainly to increased intrahepatic, presinusoidal resistance to portal blood flow. Marked splenomegaly is always seen in IPH. To clarify the pathogenetic significance of splenomegaly, immunohistochemical expression of inducible nitric oxide synthese (iNOS), endothelial NOS (eNOS), and endothelin-1 (ET-1) in spleens from patients with IPH was examined. Sinus lining cells of IPH spleens showed diffuse and strong expression of iNOS and eNOS. Sinus lining cells of spleens from patients with liver cirrhosis (LC) also showed positive signals for iNOS and eNOS, but the staining intensity was significantly weak. ET-1 was detectable in only a few mononuclear leukocytes in the red pulp of both IPH and LC spleens. These results suggest that NO liberated in spleen, rather than ET-1, is responsible for the dilatation of splenic sinuses, leading to splenomegaly, and thereby contributes to portal hypertension in IPH.