Abstract
Endothelin levels are elevated in shock, sepsis, and cholestatic jaundice, and an effect on biliary motility may be postulated. The aim of this study was to determine whether (1) endothelin-1 and endothelin-3 induce gallbladder contraction in vivo, (2) the response is caused by changes in blood pressure, and (3) the response is nerve mediated. Gallbladder pressure and blood pressure were measured in 38 anesthetized possums. Endothelin-1 or endothelin-3 (5 to 200 pmol/kg) was administered by close intra-arterial injection. Tetrodotoxin (9 μg/kg) or the mixed endothelin antagonist tezosentan was infused at a rate of 10 or 100 nmol/kg/min (close intra-arterial injection). Maximum changes in gallbladder pressure (% of carbachol-induced contraction) and blood pressure (mm Hg) were determined. Statistical analysis was carried out by means of repeated-measures analysis of variance and Kruskal-Wallis test. Both endothelin-1 and endothelin-3 induced dose-dependent increases in gallbladder pressure and blood pressure (P < 0.05), which were unaffected by pretreatment with tetrodotoxin. The endothelin-1-induced gallbladder pressure but not blood pressure was reduced by the higher dose of tezosentan (P < 0.03). The lower dose of tezosentan also produced a decrease in the endothelin-3-induced gallbladder pressure (P < 0.02) but not in blood pressure, whereas the higher dose reduced the blood pressure with no further reduction in gallbladder pressure (P < 0.05). Endothelins increase gallbladder motility in vivo, acting directly on the smooth muscle and independent of changes in blood pressure.
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References
Luscher TF, Barton M. Endothelin and endothelin receptors antagonists: Therapeutic considerations for a novel class of cardiovascular drugs. Circulation 2000;102:2434–2440.
Isales CM, Nathanson MH, Bruck R. Endothelin-1 induces cholestasis which is mediated by an increase in portal pressure. Biochem Biophys Res Commun 1993;191:1244–1251.
Kamimura Y, Sawada N, Aoki M, Mori M. Endothelin-1 induces contraction of bile canaliculi in isolated rat hepatocytes. Biochem Biophys Res Commun 1993;191:817–822.
Housset C, Carayon A, Housset B, Legendre C, Hannoun L, Poupon R. Endothelin-1 secretion by human gallbladder epithelial cells in primary culture. Lab Invest 1993 69:750–755.
Fouassier L, Chinet T, Robert B, Carayon A, Balladur P, Mergey M, Paul A, Poupon R, Capeau J, Barbu V, Housset C. Endothelin-1 is synthesized and inhibits cyclic adenosine monophosphate-dependent anion secretion by an autocrine/paracrine mechanism in gallbladder epithelial cells. J Clin Invest 1998;101:2881–2888.
Pinzani M, Milani S, De Franco R, Grappone C, Caligiuri A, Gentilini A, Tosti-Guerra C, Maggi M, Failli P, Ruocco C, Gentilini P. Endothelin 1 is overexpressed in human cirrhotic liver and exerts multiple effects on activated hepatic stellate cells. Gastroenterology 1996; 110:534–548.
Al-Jiffry BO, Meedeniya AC, Toouli J, Saccone GTP. Elevated endothelin immunoreactivity in the epithelial layer of human and possum gallbladder in-vitro [abstr]. Gastroenterology 2001; 120:A3 89.
Moummi C, Gullikson GW, Gaginella TS. Effect of endothelin-1 on guinea pig gallbladder smooth muscle in vitro. J Pharmacol Exp Ther 1992;260:549–553.
Battistini B, O’Donnell LJ, Warner TD, Fournier A, Farthing MJ, Vane JR. Characterization of endothelin (ET) receptors in the isolated gall bladder of the guinea-pig: Evidence for an additional ET receptor subtype. Br J Pharmacol 1994;112:1244–1250.
Cardozo AM, D’Orleans-Juste P, Yano M, Frank PA Jr, Rae GA. Influence of endothelin ET(A) and ET(B) receptor antagonists on endothelin-induced contractions of the guinea pig isolated gall bladder. Regul Pept 1997;69:15–23.
Huang SC, Lee MC, Wei CK, Huang SM. Endothelin receptors in human and guinea-pig gallbladder muscle. Regul Pept 2001;98:145–153.
Nora HC, Cardozo AM, D’Orleans-Juste P, Rae GA. Influences of indomethacin on contractions induced by endothelins in guinea pig isolated gallbladder. J Cardiovasc Pharmacol 2000;36(Suppl 1):S267-S269.
Cardozo AM, Koepp J, D’ Orleans-Juste P, Rae GA. Receptors mediating endothelin-1-induced contractions of rabbit gallbladder. J Cardiovasc Pharmacol 2000;36(Suppl 1):S264-S266.
Al-Jiffry BO, Meedeniya ACB, Chen JW, Toouli J, Saccone GTP. Endothelin-1 induces contraction of human and Australian possum gallbladder contraction in vitro. Regul Pept 2001;102:31–39.
Al-Jiffry BO, Toouli J, Saccone GTP. Endothelin-1: A potent stimulator of human gallbladder contraction [abstr]. J Gastroenterol Hepatol 2000;15(Suppl):J32.
Al-Jiffry BO, Toouli J, Saccone GTP. Endothelin-3 acts on endothelin-B and endothelin-A to cause potent gallbladder contraction in the Australian possum in vivo [abstr]. JHBP Surg 2001;8(Suppl):104.
Al-Jiffry BO, Menadue M, Oliver J, Thomas A, Toouli J, Saccone GTP. Endothelins in gallbladder tissue are elevated in acalculus acute cholecystitis. Gastroenterology 2002 (In press).
Cox MR, Padbury RT, Snelling TL, Schloithe AC, Harvey JR, Toouli J, Saccone GT. Gastrin-releasing peptide stimulates gallbladder motility but not sphincter of Oddi motility in Australian brush-tailed possum. Dig Dis Sci. 1998;43:1275–1284.
Pittet JF, Morel DR, Hemsen A, Gunning K, Lacroix JS, Suter PM. Elevated plasma endothelin-1 concentrations are associated with the severity of illness in patients with sepsis. Ann Surg 1991;213:261–264.
Wakiyama H, Yamashita C, Okada M, Maeda H. Increased portal endothelin-1 level is associated with the liver function after cardiopulmonary bypass in rabbits: Influence of hypothermia on the damage. Kobe J Med Sci 1997;43:245–257.
Tsai YT, Lin HC, Yang MC, Lee FY, Hou MC, Chen LS. Plasma endothelin levels in patients with cirrhosis and their relationships to the severity of cirrhosis and renal function. J Hepatol 1995;23:681–688.
Higaki I, Yamazaki O, Matsuyama M, Horii K, Kawai S, Tsukamoto T. Serum endothelin-1 and hepatocyte growth factor levels in patients with obstructive jaundice. Hepatogastroenterology 1999;46:1599–602.
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Supported in part by grant 102133 by the National Health and Medical Research Council of Australia.
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Al-Jiffry, B.O., Chen, J.W., Toouli, J. et al. Endothelins induce gallbladder contraction independent of elevated blood pressure in vivo in the australian possum. J Gastrointest Surg 6, 699–705 (2002). https://doi.org/10.1016/S1091-255X(02)00011-2
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DOI: https://doi.org/10.1016/S1091-255X(02)00011-2