Effects of prostaglandin E1alpha cyclodextrin [corrected] treatment on endothelial dysfunction in patients with systemic sclerosis

J Hypertens. 2007 Apr;25(4):793-7. doi: 10.1097/HJH.0b013e328032784f.

Abstract

Objective: Systemic sclerosis (SSc) is characterized by an altered nitric oxide (NO): endothelin I ratio and by endothelial dysfunction.

Aims: To verify the effects of prostaglandin E1 (PGE1) alpha-cyclodestrin treatment on endothelial function, quantified as flow-mediated dilation (FMD) of the radial artery.

Methods: In 16 women with SSc (age 57 +/- 2.7 years, means +/- SE) in whom a diagnosis of SSc had been made several years earlier (7.1 +/- 1.2 years), FMD was evaluated by an echotracking technique on the radial artery, using trinitroglycerin vasodilation as a non-endothelial measure of the vessel's ability to increase its diameter maximally. FMD was evaluated after 4 months washout period and after 4 months cyclic infusion of PGE1 alpha-cyclodestrin. Expired NO was measured at the same time.

Results: PGE1 alpha-cyclodestrin cyclic infusions did not modify systolic and diastolic blood pressure, heart rate or trinitroglycerin radial artery vasodilation. On the other hand, it induced a marked and significant increase in FMD of the radial artery, which was also accompanied by an increase in blood flow and expired NO.

Conclusions: Endothelial dysfunction and reduced FMD associated with SSc are improved by cyclic treatment with PGE1 alpha-cyclodestrin. This effect occurs together with a concomitant increase in expired NO, suggesting its direct positive influence on endothelial function. It may also partly explain the clinical beneficial effect of the drug in SSc.

MeSH terms

  • Alprostadil / analogs & derivatives*
  • Alprostadil / therapeutic use
  • Analysis of Variance
  • Blood Flow Velocity / drug effects
  • Blood Pressure / drug effects
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology*
  • Exhalation
  • Female
  • Heart Rate / drug effects
  • Humans
  • Infusions, Intravenous
  • Middle Aged
  • Nitric Oxide / analysis
  • Radial Artery / drug effects*
  • Radial Artery / physiopathology
  • Regional Blood Flow / drug effects
  • Scleroderma, Systemic / drug therapy*
  • Scleroderma, Systemic / metabolism
  • Scleroderma, Systemic / physiopathology*
  • Treatment Outcome
  • Vasodilation / drug effects
  • Vasodilator Agents / therapeutic use
  • alpha-Cyclodextrins / therapeutic use*

Substances

  • Vasodilator Agents
  • alpha-Cyclodextrins
  • prostaglandin E1-alpha-cyclodextrin
  • Nitric Oxide
  • Alprostadil