Effects of a phosphodiesterase-5 (PDE5) inhibitor on endothelium-dependent relaxation of myometrial small arteries

Am J Obstet Gynecol. 2004 May;190(5):1283-90. doi: 10.1016/j.ajog.2003.12.024.

Abstract

Objective: In preeclampsia, endothelium-dependent function is markedly aberrant. Myometrial resistance arteries from women with preeclampsia show a minimal, wholly nitric oxide-mediated, bradykinin-induced relaxation. Our aim was to test that phosphodiesterase 5 (PDE5) inhibition could improve endothelium-dependent function in preeclampsia. Study design Small arteries dissected from myometrial biopsies obtained at cesarean section from normal pregnant women (N=22) or women with preeclampsia (N=24) were mounted on wire or pressure myographs. Vessels were constricted (arginine vasopressin or U46619) and relaxed (bradykinin) before and after incubation with a PDE5 inhibitor, UK-343664.

Results: Endothelium-dependent vasodilatation was decreased in vessels from women with preeclampsia. 100 nmol/L UK-343664 did not affect normal pregnant but significantly improved relaxation of the vessels from women with preeclampsia.

Conclusion: A PDE5 inhibitor enhances endothelial function of myometrial vessels from women with preeclampsia, such that the behavior of these arteries approximates to those from normal women. These agents offer a potential therapeutic strategy for the management of preeclampsia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Adolescent
  • Adult
  • Arteries / drug effects
  • Biopsy
  • Case-Control Studies
  • Culture Techniques
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • Female
  • Humans
  • Middle Aged
  • Myography
  • Myometrium / blood supply*
  • Myometrium / pathology
  • Phosphoric Diester Hydrolases / drug effects*
  • Piperazines / pharmacology*
  • Pre-Eclampsia / physiopathology
  • Pregnancy
  • Pyrimidinones / pharmacology*
  • Sensitivity and Specificity
  • Uterine Contraction
  • Vasoconstrictor Agents / pharmacology*
  • Vasodilation / drug effects
  • Vasodilation / physiology

Substances

  • Piperazines
  • Pyrimidinones
  • UK 343,664
  • Vasoconstrictor Agents
  • Phosphoric Diester Hydrolases
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • PDE5A protein, human