Phosphodiesterase-5 inhibitors and omental and placental small artery function in normal pregnancy and pre-eclampsia Mark Wareing a, * , Jenny E. Myers a , Maureen O’Hara a , Louise C. Kenny a , Michael J. Taggart a , Laurence Skillern b , Ian Machin b , Philip N. Baker a a Maternal and Fetal Health Research Centre, St. Mary’s Hospital, University of Manchester, Hathersage Road, Manchester M130JH, UK b Pfizer Limited, Ramsgate Road, Sandwich, UK Received 13 January 2004; received in revised form 21 April 2004; accepted 13 June 2004 Abstract Objectives: 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. Study design: 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 1 h 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. Conclusion: Use of PDE5 inhibitors does not significantly alter endothelial-dependent relaxation in omental or placental small arteries from PE women. # 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Pre-eclampsia; Phosphodiesterase-5 inhibitors; Human; Omentum; Placenta 1. Introduction Pre-eclampsia is a complicating factor affecting 2–3% of primigravidae pregnancies in the United Kingdom and is a major cause of perinatal and maternal morbidity [1]. The pathophysiology of pre-eclampsia is thought to involve two interlinked processes: a failure of spiral artery transforma- tion in early pregnancy which leads to a hypo-perfused uteroplacental unit [2,3] and the subsequent release of a factor(s) from the placenta that promotes activation of the maternal vascular endothelium [4,5]. Endothelial involve- ment/activation in pre-eclampsia is well documented with a number of markers of endothelial cell activation being increased in women with pre-eclampsia [2,3,6–11]. Aberrant endothelium-dependent responses have been demonstrated in a variety of blood vessels from women with pre-eclampsia, compared to vessels isolated from normal pregnant women [12–16]. McCarthy et al. [12] found attenuated endothelial-dependent vasodilatation in subcu- taneous vessels from women with pre-eclampsia, a finding supported by Knock and Poston [15] and by Cockell and Poston [14] who demonstrated impaired flow-induced release of nitric oxide in human subcutaneous small arteries from women with pre-eclampsia using the technique of pressure myography. Similarly attenuated endothelium- dependendent vasodilatation has been demonstrated in myometrial [13] and omental [16] small arteries from www.elsevier.com/locate/ejogrb European Journal of Obstetrics & Gynecology and Reproductive Biology 127 (2006) 41–49 * Corresponding author. Tel.: +44 161 276 5474; fax: +44 161 276 6134. E-mail address: mark.wareing@man.ac.uk (M. Wareing). 0301-2115/$ – see front matter # 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2004.06.014