Phosphodiesterase-5 inhibitors and omental and placental small artery function in normal pregnancy and pre-eclampsia.
OBJECTIVE
In pre-eclampsia (PE), endothelium-dependent function of myometrial small arteries is markedly attenuated. The residual PE response is wholly NO mediated. We have previously demonstrated that PDE5 inhibition can improve endothelial function in myometrial small arteries from women with PE. We aimed to assess whether the effect of PDE5 inhibition in PE was myometrial artery specific.


METHODS
Small arteries were dissected from omental biopsies obtained at Caesarean section from normal pregnant women (NP, N = 20) and women with PE (N = 11). Chorionic plate small arteries were dissected from NP (N = 13) and PE (N = 11) placentae. Vasoconstriction (arginine vasopressin or thromboxane-mimetic U46619) and endothelial-dependent relaxation were assessed by wire and pressure myography. Constriction/relaxation curves were repeated post 1h incubation with PDE5 inhibitors UK-343664 or sildenafil citrate (0, 10 or 100 nM).


RESULTS
Omental artery constriction was increased in PE. Omental vessel constriction was unaffected by PDE5 inhibition. Sildenafil citrate improved bradykinin-induced but not acetylcholine-induced relaxation of omental small arteries from NP women. PDE5 inhibition did not alter relaxation of omental arteries from women with PE. Placental small arteries were unaffected by PDE5 inhibition.


CONCLUSIONS
Use of PDE5 inhibitors does not significantly alter endothelial-dependent relaxation in omental or placental small arteries from PE women.
Wareing
Mark
M
Maternal and Fetal Health Research Centre, St. Mary's Hospital, University of Manchester, Hathersage Road, Manchester M130JH, UK. mark.wareing@man.ac.uk
Myers
Jenny E
JE
O'Hara
Maureen
M
Kenny
Louise C
LC
Taggart
Michael J
MJ
Skillern
Laurence
L
Machin
Ian
I
Baker
Philip N
PN
D000704:Analysis of Variance; D001160:Arterioles / Q000187:drug effects*; D001706:Biopsy; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D009213:Myography; D009215:Myometrium / Q000098:blood supply; D009852:Omentum / Q000098:blood supply*; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply*; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000503:physiopathology*; D011247:Pregnancy / Q000502:physiology*; D011687:Purines / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology; D016896:Treatment Outcome; D014590:Uterine Contraction; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011744:Pyrimidinones; D013450:Sulfones; C450961:UK 343,664; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate