pyrimidinones and Pre-Eclampsia

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.. 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).. 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.. Use of PDE5 inhibitors does not significantly alter endothelial-dependent relaxation in omental or placental small arteries from PE women.

Topics: Analysis of Variance; Arterioles; Biopsy; Case-Control Studies; Endothelium, Vascular; Female; Humans; Myography; Myometrium; Omentum; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Placenta; Pre-Eclampsia; Pregnancy; Purines; Pyrimidinones; Sildenafil Citrate; Sulfones; Treatment Outcome; Uterine Contraction; Vasodilation; Vasodilator Agents

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.. 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.. 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.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adolescent; Adult; Arteries; Biopsy; Case-Control Studies; Culture Techniques; Cyclic Nucleotide Phosphodiesterases, Type 5; Endothelium, Vascular; Female; Humans; Middle Aged; Myography; Myometrium; Phosphoric Diester Hydrolases; Piperazines; Pre-Eclampsia; Pregnancy; Pyrimidinones; Sensitivity and Specificity; Uterine Contraction; Vasoconstrictor Agents; Vasodilation