Ursodeoxycholic acid and endothelial-dependent, nitric oxide-independent vasodilatation of forearm resistance arteries in patients with coronary heart disease

Br J Clin Pharmacol. 1999 Jun;47(6):661-5. doi: 10.1046/j.1365-2125.1999.00940.x.

Abstract

Aims: Ursodeoxycholic acid (UDCA) has cholesterol lowering and anti-inflammatory effects and bile acids are reported to exert vasodilator effects; all of these properties might be considered desirable in a drug used in the treatment of patients with coronary heart disease. We investigated a hypothesis that UDCA may dilate arteries and the mechanism of action.

Methods: We evaluated effects of a 6-week treatment with UDCA in 11 coronary heart disease patients on endothelium-dependent (acetylcholine-induced) and -independent (nitroprusside-induced) vasodilatations in forearm vasculature by strain-gauge plethysmography. Healthy individuals (n=14) served as baseline controls.

Results: The percentage increase by acetylcholine in the flow of the infused arm relative to the non-infused arm of coronary heart disease patients during the trial remained unaltered, but vasodilatation to NG-monomethyl-l-arginine+acetylcholine was improved by 161+/-27% with UDCA vs 83+/-22% with placebo (mean difference 91% [95% CI 35%, 147%], P=0.016).

Conclusions: Six weeks' UDCA therapy improved endothelium-dependent nitric oxide-independent vasodilatation, which might maintain arterial flow in coronary heart disease patients under conditions of impaired nitric oxide production.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Adult
  • Aged
  • Coronary Disease / drug therapy*
  • Coronary Disease / physiopathology
  • Cross-Over Studies
  • Double-Blind Method
  • Endothelium, Vascular / physiology*
  • Female
  • Forearm / blood supply*
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide / physiology*
  • Ursodeoxycholic Acid / adverse effects
  • Ursodeoxycholic Acid / pharmacology
  • Ursodeoxycholic Acid / therapeutic use*
  • Vasodilation / drug effects*
  • omega-N-Methylarginine / pharmacology

Substances

  • omega-N-Methylarginine
  • Nitric Oxide
  • Ursodeoxycholic Acid
  • Acetylcholine