Abstract
Previous studies from our laboratory suggest that humoral factors, namely glucagon, can account for approximately 30% of the splanchnic vasodilation in rats with prehepatic portal hypertension. A reduced vascular sensitivity to norepinephrine, vasopressin, and angiotensin II may contribute to the splanchnic vasodilation. However, neither glucagon nor an altered vasoconstrictor sensitivity can fully account for the splanchnic vasodilation observed in portal hypertensive subjects. Therefore, the present study was designed to examine the role of bile acids in the splanchnic hyperemia of portal hypertension since (1) serum bile acids are elevated in portal hypertensive subjects and (2) bile acids are potent intestinal vasodilators. Prehepatic portal hypertension was induced in Sprague-Dawley rats by surgical constriction of the portal vein. Ten to 14 days after the induction of portal hypertension, the enterohepatic circulation of control and portal hypertensive rats was surgically interrupted. The animals were placed in Bollman restraint cages and allowed to recover. Eighteen to 24 hr later, the rats were anesthetized with sodium pentobarbital and regional blood flow measured with radiolabeled microspheres. Normal and portal hypertensive animals without bile fistula served as controls. Plasma bile acid levels measured by radioimmunoassay were approximately 3.8 times higher in portal hypertensive animals than in control. Bile duct cannulation effectively depleted both normal and portal hypertensive animals of their circulating bile acid pool and significantly reduced portal venous inflow in portal hypertensive but not in control rats. A role for bile acids as partial mediators of the splanchnic hyperemia of portal hypertension is suggested since bile acid depletion did not completely abolish the gastrointestinal hyperemia.
Similar content being viewed by others
References
Benoit JN, Barrowman JA, Harper SL, Kvietys PR, Granger DN: Role of humoral factors in the intestinal hyperemia associated with chronic portal hypertension. Am J Physiol 247(10):G486-G493, 1984
Benoit JN, Zimmerman B, Premen AJ, Go VLW, Granger DN: Role of glucagon in the splanchnic hyperemia of chronic portal hypertension. Am J Physiol 251(14):G674-G677, 1986
Korthuis, RJ, Benoit JN, Kvietys PR, Townsley MI, Taylor AE, Granger DN: Humoral factors may mediate increased rat hindquarter blood flow in portal hypertension. Am J Physiol 249:H827-H833, 1985
Kravetz D, Bosch J, Arderiu MT, Pizcueta MP, Casamitjana R, Rivera F, Rodes J: Effects of somatostatin on splanchnic hemodynamics and plasma glucagon in portal hypertensive rats. Am J Physiol 254:G322-G328, 1988
Blanchart A, Hernando N, Fernando-Munoz D, Hernando L, Lopez-Novoa JM: Lack of effect of indomethacin on systemic and splanchnic hemodynamics in portal hypertensive rats. Clin Sci 68:605–607, 1985
Bomzon A, Finberg JPM, Tovbin D, Naidu SG, Better OS: Bile salts, hypotension and obstructive jaundice. Clin Sci 67:177–183, 1984
Ohkubo H, Okuda K, Iida S, Ohnishi K, Ikawa S, Makim I: Role of portal and splenic vein shunts and impaired hepatic extraction in the elevated serum bile acids in liver cirrhosis. Gastroenterology 86:514–520, 1984
Kvietys PR, McLendon JM, Granger DN: Postprandial intestinal hyperemia: Role of bile salts in the ileum. Am J Physiol 241(4):G469-G477, 1981
Chojkier M, Groszmann RJ: Measurement of portal-systemic shunting in the rat by using gamma-labeled microspheres. Am J Physiol 240:G371-G375, 1981
Benoit JN, Womack WA, Hernandez L, Granger DN: “Forward” and “backward” flow mechanisms of portal hypertension, Relative contributions in the rat model of portal vein stenosis. Gastroenterology 89:1092–1096, 1985
Cummings SA, Groszmann RJ, Kaumann AJ: Hypersensitivity of mesenteric veins to 5-hydroxytryptamine and ketanserin-induced reduction of portal pressure in portal hypertensive rats. Br J Pharmacol 89:501–513, 1986
Murray BM, Paller MS: Pressor resistance to vasopressin in sodium depletion, potassium depletion and cirrhosis. Am J Physiol 251:R525-R530, 1986
Murray BM, Paller MS: Decreased pressor reactivity to angiotensin II in cirrhotic rats: Evidence for a post receptor defect in angiotensin action. Circ Res 57:424–431, 1985
Sherwin R, Joshi P, Hendler R, Felig P, Conn HO: Hyperglucagonemia in Laennec's cirrhosis. N Engl J Med 290:239–242, 1974
Villamediana LM, Sanz E, Fernandez-Gallardo S, Caramelo C, Sanchez Crespo M, Braquet P, Lopez-Novoa JM: Effects of the platelet-activating factor antagonist BN-52021 on the hemodynamics of rats with experimental cirrhosis of the liver. Life Sci 39:201–205, 1986
Harper SL, Kvietys PR, Granger DN: Role of tissuePo 2 in the bile salt-induced ileal hyperemia. Gastroenterology 90(5):1450, 1986
Bomzon A, Gali D, Better OS, Blendis LM: Reversible suppression of the vascular contractile response in rats with obstructive jaundice. J Lab Clin Med 105:568–572, 1985
Bomzon A, Blendis LM: Vascular reactivity in experimental portal hypertension. Am J Physiol 252(15):G158-G162, 1987
Kiel JW, Pitts V, Benoit JN, Granger DN, Shepherd AP: Reduced vascular sensitivity to norepinephrine in portal hypertensive rats. Am J Physiol 248:G192-G195, 1985
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Thomas, S.H., Joh, T. & Benoit, J.N. Role of bile acids in splanchnic hemodynamic response to chronic portal hypertension. Digest Dis Sci 36, 1243–1248 (1991). https://doi.org/10.1007/BF01307516
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01307516