• Bile salts;
  • vascular smooth muscle;
  • calcium channels;
  • taurodeoxycholate;
  • haemodynamics;
  • cirrhosis;
  • splanchnic circulation
  • 1
    The vasoactive mechanisms of bile salts have been investigated in rat isolated portal venous and superior mesenteric arterial rings and perfused mesentery.
  • 2
    The isolated perfused mesentery was precontracted with a selective α1-adrenoceptor agonist, cirazoline. Incremental doses of tauroursodeoxycholate (TUDC), taurochenodeoxycholate (TCDC) and taurodeoxycholate (TDC) caused a dose-dependent vasorelaxation. The order of potency of the vasodilator effect was TDC > TCDC > TUDC.
  • 3
    The effect of TDC (1.9 × 10−8 −1.9 × 10−6 mol) was examined before and after propranolol (3 μm), tetraethylammonium (5 mM), ouabain (10−5 M), NG-nitro-l-arginine methyl ester (10−4 M) and capsaicin (50 mg kg−1) to block, respectively, β-adrenoceptors, K+-channels, Na+, K+-ATPase, nitric oxide synthase, and primary sensory nerves. The vasodilator effect of TDC was not affected by any of these blocking agents or by denuding vascular endothelium with distilled water.
  • 4
    Infusion of TDC (1.9 × 10−8 −1.9 × 10−6 mol) with K+-free or high K+ (60 mM) physiological salt solution (PSS) did not affect the vasodilator effect of TDC.
  • 5
    Contractions induced by KCl (0.01–1.0 M), arginine vasopressin (AVP, 10−10 −10−7 M) or cirazoline (10−7 × 10−5 M) were all inhibited by TDC (300 μm).
  • 6
    TDC (10−6 to 10−3 M) also inhibited the basal tension and the development of spontaneous contractions in the isolated portal vein.
  • 7
    TDC (300 μm), however, did not affect noradrenaline-induced phasic contractions elicited in Ca2+-free PSS by Ca2+ release from intracellular stores.
  • 8
    We conclude that TDC inhibits Ca2+ entry through both voltage-operated and receptor-operated calcium channels, whereas intracellular Ca2+ release is not affected.