Abstract
This study investigated the effects of portal hypertension on gastric motor and secretory functions and the role of endothelin in rats. Control; sham-operated; endothelin-A receptor blocker, BQ 485 (1 µg/kg) -treated; portal hypertensive; and portal hypertension +, endothelin-A receptor blocker-treated rats were subjected to tests of gastric secretory, motor, and mucosal function studies as well as gastric wall polymorphonuclear infiltration. Portal hypertension was induced by partial portal vein ligation. Portal hypertension suppressed gastric acid and total fluid secretion and delayed gastric emptying. An increase in mucosal permeability and no alteration in gastric wall myeloperoxydase activity were observed. The effects of portal hypertension on gastric secretory, motor, and mucosal functions were reversed by treatment with endothelin-A receptor blocker, BQ-485. It is concluded that portal hypertension suppresses the gastric motor and secretory functions and endothelin plays an important role in the pathophysiology of gastric alterations associated with portal hypertension.
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Baxter JN, Dobbs BR: Portal hypertensive gastropathy. J Gastroenterol Hepatol 3:635–644, 1988
Dobbs BR, Hider RN, Baxter JN: Structural and functional changes of the gastric mucosa in rats with portal hypertension. J Gastroenterol Hepatol 6:350–354, 1991
Ma JJ, Cho CH, Ogle CW: Portal hypertension. Its effects on gastric function and ethanol-induced gastric mucosal damage in rats. Dig Dis Sci 38:2203–2208, 1993
Sherlock S: Hepatic cirrhosis.In Diseases of the Liver and Biliary System, 8th ed. Oxford, Blackwell Scientific Publications, 1989, pp 410–424
Chesta J, Lillo R, Defilippi C, Velasco M, Katz R: Orocecal transit time and gastric emptying in patients with cirrhosis. Gastroenterology 100:A43, 1991
Yanagisawa M: A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415, 1988
Takahashi K, Jones PM, Kanse SM, Lam HC, Spokes RA, Ghatei MA, Bloom SR: Endothelin in the gastrointestinal tract. Presence of endothelin-like immunoreactivity, messenger RNA, endothelin receptors, and pharmacological effect. Gastroenterology 99:1660–1667, 1990
Kitsukawa Y, Gu ZF, Hildebrand P, Jensen RT: Gastric smooth muscle cells possess two classes of endothelin receptors but only one alters contractions. Am J Physiol 66:G713-G721, 1994
Inagashi H, Bishop AE, Escrig C, Wharton J, Allen-Mersh TG, Polak JM: Localisation of endothelin-like immunoreactivity and endothelin binding sites in human colon. Gastroenterology 101:47–54, 1991
Yoshinaga M, Chijiwa Y, Misawa T, Harada NN, Nawata H: Endothelin-B receptor on guinea pig small intestinal smooth muscle cells. Am J Physiol 262:G308-G311, 1992
Uchihara M, Izumi N, Sato C, Marumo F: Clinical significance of elevated plasma endothelin concentration in patients with cirrhosis. Hepatology 16:95–99, 1992
Asbert M, Gines A, Gines P, Jimenes W, Claria J, Salo J, Arroyo V, Francisca R, Rodes J: Circulating levels of endothelin in cirrhosis. Gastroenterology 104:1485–1491, 1993
Yu PC, Kuo JS, Lin HC, Yang MCM: Effects of endothelin in portal hypertensive rats. Clin Sci 83:165–170, 1992
Isobe H, Sakai H, Satoh M, Sakamoto S, Nawata H: Delayed gastric emptying in patients with liver cirrhosis. Dig Dis Sci 39:983–987, 1994
Galati JS, Holdeman KP, Dalrymple GV, Harrison KA, Quigley EMM: Delayed gastric emptying in patients both liquid and solid components of a meal in chronic liver disease. Am J Gastroenterol 89:708–711, 1994
Scarpignato C, Capovilla T, Bertaccini G: Action on gastric emptying of conscious rat. Arch Int Pharmacodyn 246:286–294, 1980
Coşkun T, Sevinç A, Tevetoğlu İ, Alican İ, Kurtel H, Yeğen BÇ: Delayed gastric emptying in conscious male rats following estrogen and progesterone treatment. Res Exp Med 195:49–54, 1995
Wang WSF, Rahwan RG: Antiulcer activity of the calcium antagonist propymethylene-dioxyindene-11. Effects on acid secretion and gastric emptying in rats. Clin Pharmacol 21:327–331, 1990
Levine RL, Garland D, Oliver CN: Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–478, 1990
Suzuki K, Hiromo O, Sasgawa S, Sakatani T, Fujikara T: Assay method for myeloperoxidase in human polymorphonuclear leukocytes. Ann Biochem 13:345–352, 1983
Tally NJ, Shuter B, McCrudden G, Jones M, Hoschl R, Piper DW: Lack of association between gastric emptying of solids and symptoms in nonulceer dyspepsia. J Clin Gastroenterol 11:625–630, 1989
Vorobioff J, Bredfeldt JE, Groszmann RJ: Hyperdynamic circulation in portal hypertensive rat model: A primary factor for maintenance of chronic portal hypertension. Am J Physiol 244:G52-G57, 1983
Benoit JN, Granger DN: Splanchnic hemodynamics in chronic portal hypertension. Semin Liver Dis 6:287–289, 1986
Beutler JJ, Koomans HA, Rabelink YJ: Blunted natriuretic response and low blood pressure after atrial natriuretic factor in early cirrhosis. Hepatology 10:148–153, 1989
Vallance P, Moncada S: Hyperdynamic circulation in cirrhosis: A role for nitric oxide? Lancet 337:776–778, 1991
Pizcueta MP, Casamitjana R, Bosh J, Rodes J: Decreased vascular sensitivity to norepinephrine in portal hypertensive rats: Role of hyperglucagonism. Am J Physiol 258:G191-G195, 1990
Itoh S, Sasaki T, Katsuhisa I, Ishikawa K, Nishikibe M, Yaro M: A novel endothelin ETA receptor antagonist, BQ 485, and its preservative effect in experimental cerebral vasospasm in dogs. Biochem Biophys Res Commun 195:969–975, 1993
Wallace JL, Giuseppe C, DeNucci G, McKnight W, Mac-Naughton WK: Endothelin has potent ulcerogenic and vasoconstrictor actions in the stomach. Am J Physiol 256:G661-G666, 1989
Wallace JL, Keenan CM, MacNaughton WK, McKnight GW: Comparison of the effects of endothelin 1 and endothelin 3 in the rat stomach. Eur J Pharmacol 167:41–47, 1989
Rubanyi GM, Polokoff MA: Endothelins: Molecular biology, biochemistry pharmacology, physiology and pathophysiology. Pharm Rev 46:325–415, 1994
Claria J, Jimenez W, Ros J: Pathogenesis of arterial hypotension in cirrhotic rats with ascites: Role of endogenous nitric oxide. Hepatology 15:343–349, 1992
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Günal, Ö., Yeğen, C., Özdemir Aktan, A. et al. Gastric functions in portal hypertension. Digest Dis Sci 41, 585–590 (1996). https://doi.org/10.1007/BF02282345
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DOI: https://doi.org/10.1007/BF02282345