Mechanism of bile salt vasoactivity: dependence on calcium channels in vascular smooth muscle

Jung‐Min ‐M Pak, Ayotunde S.O. Adeagbo, Christopher R. Triggle, Eldon A. Shaffer, Samuel S. Lee

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The vasoactive mechanisms of bile salts have been investigated in rat isolated portal venous and superior mesenteric arterial rings and perfused mesentery. 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. 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. 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. 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). TDC (10−6 to 10−3 M) also inhibited the basal tension and the development of spontaneous contractions in the isolated portal vein. TDC (300 μm), however, did not affect noradrenaline‐induced phasic contractions elicited in Ca2+‐free PSS by Ca2+ release from intracellular stores. We conclude that TDC inhibits Ca2+ entry through both voltage‐operated and receptor‐operated calcium channels, whereas intracellular Ca2+ release is not affected. 1994 British Pharmacological Society

Original languageEnglish
Pages (from-to)1209-1215
Number of pages7
JournalBritish Journal of Pharmacology
Volume112
Issue number4
DOIs
Publication statusPublished - Aug 1994

    Fingerprint

Keywords

  • Bile salts
  • calcium channels
  • cirrhosis
  • haemodynamics
  • splanchnic circulation
  • taurodeoxycholate
  • vascular smooth muscle

ASJC Scopus subject areas

  • Pharmacology

Cite this