Hyperglucagonemia and hyperdynamic circulation in rats with biliary cirrhosis

Glucagon, a hormone with a potent vasodilatory action, has been suggested to play a role in the hyperkinetic circulation in animals with portocaval shunts and chronic portal venous stenosis; however, its role in cirrhosis has not been examined. We tested the hypothesis that increased levels of circulating glucagon contribute to the hyperdynamic circulatory state found in rats with biliary cirrhosis. Compared with plasma glucagon levels in sham-operated controls, glucagon levels, measured by radioimmunoassay, were significantly increased in chronic bile duct-ligated (5 to 6 weeks) cirrhotic rats (603 +/- 107 pg/ml vs 197 +/- 11 pg/ml, p < 0.001) but not in acute bile duct-ligated (10 days) cholestatic rats (310 +/- 55 pg/ml). Unanesthetized, catheter-implanted cirrhotic--but not cholestatic--rats exhibited a hyperdynamic circulatory state with increased cardiac index and decreased systemic vascular resistance. The plasma glucagon level correlated with cardiac index (r = 0.62, p < 0.01) and systemic vascular resistance (r = -0.54, p < 0.05). In addition, cirrhotic rats showed depressed hypoxic pulmonary vasoconstriction that was correlated with increased plasma glucagon level (r = -0.68, p < 0.01). We conclude that circulating glucagon is increased in rats with biliary cirrhosis and that hyperglucagonemia may contribute to the observed systemic hyperdynamic circulatory state and the loss of hypoxic pulmonary vasoconstriction in these rats.