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 hyperdynam ic circulation of cirrhosis, we studied the vasoactive effects of thre e different bile salts - tauroursodeoxycholic acid, taurochenodeoxycho lic acid and taurodeoxycholic acid-in cirrhotic rats. Cirrhosis was in duced with bile duct ligation; controls underwent sham surgery. In viv o, 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 . 100 gm-1 . min-1) for 5 min. Taurochenodeoxycholic acid and taurodeoxycholic acid infusions increased mesenteric arterial blood flow and conductance and induced s ystemic arterial hypotension, whereas tauroursodeoxycholic acid had no significant effect. At similar plasma levels of bile salts, the respo nses 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) w ere measured. In all three vessels, taurodeoxycholic acid produced str onger dilatory effects than did taurochenodeoxycholic acid, whereas ta uroursodeoxycholic acid showed no significant effect. Vessels from cir rhotic and control rats did not differ in degree of response. These re sults indicate that bile salts are directly vasoactive and can induce splanchnic vasodilation at the pathophysiological plasma levels seen i n cirrhosis. Bile salts may be involved in the pathogenesis of splanch nic hyperemia and hyperdynamic circulation in cirrhosis.