Vasoactive effects of bile salts in cirrhotic rats: in vivo and in vitro studies

To clarify a possible pathogenic role for bile salts in the hyperdynamic circulation of cirrhosis, we studied the vasoactive effects of three different bile salts-tauroursodeoxycholic acid, taurochenodeoxycholic acid and taurodeoxycholic acid-in cirrhotic rats. Cirrhosis was induced with bile duct ligation; controls underwent sham surgery. In vivo, the bile salts were intravenously infused at one of three doses (1.2 x 10(-7), 1.2 x 10(-6) and 6.0 x 10(-5) mol x 100 gm-1 x min-1) for 5 min. Taurochenodeoxycholic acid and taurodeoxycholic acid infusions increased mesenteric arterial blood flow and conductance and induced systemic arterial hypotension, whereas tauroursodeoxycholic acid had no significant effect. At similar plasma levels of bile salts, the responses in cirrhotic rats were attenuated compared with those of controls. In vitro, isolated rings of superior mesenteric and carotid arteries and portal vein were precontracted with phenylephrine; then dilatory responses to cumulative doses of bile salts (10(-6) to 10(-3) mol/L) were measured. In all three vessels, taurodeoxycholic acid produced stronger dilatory effects than did taurochenodeoxycholic acid, whereas tauroursodeoxycholic acid showed no significant effect. Vessels from cirrhotic and control rats did not differ in degree of response. These results indicate that bile salts are directly vasoactive and can induce splanchnic vasodilation at the pathophysiological plasma levels seen in cirrhosis. Bile salts may be involved in the pathogenesis of splanchnic hyperemia and hyperdynamic circulation in cirrhosis.