Mechanism of bile salt vasoactivity: dependence on calcium channels in vascular smooth muscle
Article first published online: 19 JUL 2012
1994 British Pharmacological Society
British Journal of Pharmacology
Volume 112, Issue 4, pages 1209–1215, August 1994
How to Cite
Pak, J.-M., Adeagbo, A. S.O., Triggle, C. R., Shaffer, E. A. and Lee, S. S. (1994), Mechanism of bile salt vasoactivity: dependence on calcium channels in vascular smooth muscle. British Journal of Pharmacology, 112: 1209–1215. doi: 10.1111/j.1476-5381.1994.tb13212.x
- Issue published online: 19 JUL 2012
- Article first published online: 19 JUL 2012
- Received February 16, 1994; Revised April 14, 1994; Accepted April 18, 1994
- Bile salts;
- vascular smooth muscle;
- calcium channels;
- splanchnic circulation
- 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.