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


CONCLUSIONS
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.
Wareing
Mark
M
Maternal and Fetal Health Research Centre, The University of Manchester, St Mary's Hospital, Manchester, United Kingdom. mark.wareing@man.ac.uk
Myers
Jenny E
JE
O'hara
Maureen
M
Kenny
Louise C
LC
Warren
Averil Y
AY
Taggart
Michael J
MJ
Skillern
Laurence
L
Machin
Ian
I
Baker
Philip N
PN
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000293:Adolescent; D000328:Adult; D001158:Arteries / Q000187:drug effects; D001706:Biopsy; D016022:Case-Control Studies; D046508:Culture Techniques; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009213:Myography; D009215:Myometrium / Q000098:blood supply* / Q000473:pathology; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011225:Pre-Eclampsia / Q000503:physiopathology; D011247:Pregnancy; D011744:Pyrimidinones / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D014590:Uterine Contraction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D010879:Piperazines; D011744:Pyrimidinones; C450961:UK 343,664; D014662:Vasoconstrictor Agents; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human