Mechanism of bile salt vasoactivity: dependence on calcium channels in vascular smooth muscle
Liver Unit, GI Research Group, University of Calgary Faculty of Medicine, 3330 Hospital Dr. NW, Calgary, AB Canada T2N 4N1
- 1The vasoactive mechanisms of bile salts have been investigated in rat isolated portal venous and superior mesenteric arterial rings and perfused mesentery.
- 2The 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.
- 3The 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.
- 4Infusion 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.
- 5Contractions 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).
- 6TDC (10−6 to 10−3 M) also inhibited the basal tension and the development of spontaneous contractions in the isolated portal vein.
- 7TDC (300 μm), however, did not affect noradrenaline-induced phasic contractions elicited in Ca2+-free PSS by Ca2+ release from intracellular stores.
- 8We conclude that TDC inhibits Ca2+ entry through both voltage-operated and receptor-operated calcium channels, whereas intracellular Ca2+ release is not affected.