Ursodeoxycholic acid and endothelial-dependent, nitric oxide-independent vasodilatation of forearm resistance arteries in patients with coronary heart disease.
OBJECTIVE
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.
Sinisalo
J
J
Helsinki University Central Hospital, Department of Medicine, Division of Cardiology, Helsinki, Finland.
Vanhanen
H
H
Pajunen
P
P
Vapaatalo
H
H
Nieminen
M S
MS
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology*; D014580:Ursodeoxycholic Acid / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D014580:Ursodeoxycholic Acid; D000109:Acetylcholine