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

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Abstract

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.

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References

  1. Nakanuma Y, Tsuneyama K, Ohbu M, Katayanagi K (2001) Pathology and pathogenesis of idiopathic portal hypertension with an emphasis on the liver. Pathol Res Pract 197:65–76

    Article  PubMed  CAS  Google Scholar 

  2. Nakanuma Y, Hoso M, Sasaki M, Terada T, Katayanagi K, Nonomura A, Kurumaya H, Harada A, Obata H (1996) Histopathology of the liver in noncirrhotic portal hypertension of unknown aetiology. Histopathology 28:195–204

    Article  PubMed  CAS  Google Scholar 

  3. Okudaira M, Ohbu M, Okuda K (2002) Idiopathic portal hypertension and its pathology. Semin Liver Dis 22:59–72

    Article  PubMed  Google Scholar 

  4. Okuda K, Kono K, Ohnishi K, et al. (1984) Clinical study of eighty-six cases of idiopathic portal hypertension and comparison with cirrhosis with splenomegaly. Gastroenterology 86:600–610

    PubMed  CAS  Google Scholar 

  5. Tsuneyama K, Ohba K, Zen Y, Sato Y, Niwa H, Minato H, Nakanuma Y (2003) A comparative histological and morphometric study of vascular changes in idiopathic portal hypertension and alcoholic fibrosis/cirrhosis. Histopathology 43:55–61

    Article  PubMed  CAS  Google Scholar 

  6. Tsuneyama K, Kouda W, Nakanuma Y (2002) Portal and parenchymal alterations of the liver in idiopathic portal hypertension: a histological and immunochemical study. Pathol Res Pract 198:597–603

    Article  PubMed  Google Scholar 

  7. Dhiman RK, Chawla Y, Vasishta RK, Kakkar N, Dilawari JB, Trehan MS, Puri P, Mitra SK, Suri S (2002) Noncirrhotic portal fibrosis (idiopathic portal hypertension): experience with 151 patients and a review of the literature. J Gastroenterol Hepatol 17:6–16

    Article  PubMed  Google Scholar 

  8. Maesawa C, Sakuma T, Sato T, Masuda T, Muro-oka G, Satodate R (1995) Structural characteristic of splenic sinuses in idiopathic portal hypertension. Pathol Int 45:642–648

    PubMed  CAS  Google Scholar 

  9. Akahoshi T, Hashizume M, Tanoue K, Shimabukuro R, Gotoh N, Tomikawa M, Sugimachi K (2002) Role of the spleen in liver fibrosis in rats may be mediated by transforming growth factor beta-1. J Gastroenterol Hepatol 17:59–65

    Article  PubMed  CAS  Google Scholar 

  10. Kaido T, Oe H, Yoshikawa A, Okajima A, Imamura M (2004) Expressions of molecules associated with hepatocyte growth factor activation after hepatectomy in liver cirrhosis. Hepatogastroenterology 51:547–551

    PubMed  CAS  Google Scholar 

  11. Rockey D (1997) The cellular pathogenesis of portal hypertension: stellate cell contractility, endothelin, and nitric oxide. Hepatology 25:2–5

    Article  PubMed  CAS  Google Scholar 

  12. Wiest R, Groszmann RJ (1999) Nitric oxide and portal hypertension: its role in the regulation of intrahepatic and splanchnic vascular resistance. Semin Liver Dis 19:411–426

    Article  PubMed  CAS  Google Scholar 

  13. Farzaneh-Far R, Moore K (2001) Nitric oxide and the liver. Liver 21:161–174

    Article  PubMed  CAS  Google Scholar 

  14. Inoue A, Yanagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K, Masaki T (1989) The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci USA 86:2863–2867

    Article  PubMed  CAS  Google Scholar 

  15. Nagasue N, Dhar DK, Yamanoi A, Emi Y, Udagawa J, Yamamoto A, Tachibana M, Kubota H, Kohno H, Harada T (2000) Production and release of endothelin-1 from the gut and spleen in portal hypertension due to cirrhosis. Hepatology 31:1107–1114

    Article  PubMed  CAS  Google Scholar 

  16. Ohara N, Futagawa S, Watanabe S, Fukasawa M, Takamori S (2001) Clinical investigation of endothelin-1 and nitric oxide in patients with portal hypertension focusing on plasma levels and immunohistological staining of liver tissues. Hepatol Res 21:40–54

    Article  PubMed  CAS  Google Scholar 

  17. Yamamoto K (1978) Morphological studies of the spleen in splenomegalic liver cirrhosis comparing with the spleen in idiopathic portal hypertension (so-called Banti’s syndrome without liver cirrhosis). Acta Pathol Jpn 28:891–905

    PubMed  CAS  Google Scholar 

  18. Cavalli G, Re G, Casali AM, Monari P (1982) The microvascular architecture of spleen in congestive splenomegaly. A morphological-histometric study. Pathol Res Pract 174:131–146

    CAS  Google Scholar 

  19. Suzuki T (1972) Application of scanning electron microscopy in the study of the human spleen: three dimensional fine structure of the normal red pulp and its changes as seen in splenomegalias associated with Banti’s syndrome and cirrhosis of the liver. Nippon Ketsueki Gakkai Zasshi 35:506–522

    PubMed  CAS  Google Scholar 

  20. Moncada S, Higgs A (1993) The L-arginine-nitric oxide pathway. N Engl J Med 329:2002–2012

    Article  PubMed  CAS  Google Scholar 

  21. Kamath PS, Carpenter HA, Lloyd RV, McKusick MA, Steers JL, Nagorney DM, Miller VM (2000) Hepatic localization of endothelin-1 in patients with idiopathic portal hypertension and cirrhosis of the liver. Liver Transpl 6:596–602

    Article  PubMed  CAS  Google Scholar 

  22. Blendis L, Wong F (2001) The hyperdynamic circulation in cirrhosis: an overview. Pharmacol Ther 89:221–231

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Yasuni Nakanuma.

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Sato, Y., Sawada, S., Kozaka, K. et al. Significance of Enhanced Expression of Nitric Oxide Syntheses in Splenic Sinus Lining Cells in Altered Portal Hemodynamics of Idiopathic Portal Hypertension. Dig Dis Sci 52, 1987–1994 (2007). https://doi.org/10.1007/s10620-006-9146-9

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  • DOI: https://doi.org/10.1007/s10620-006-9146-9

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