Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Involvement of prostaglandin F 2a in preeclamptic human umbilical vein vasospasm: a role of prostaglandin F and thromboxane A 2 receptors Gokce Topal a , Nabil Foudi b , B. Sonmez Uydes-Dogan a , Thierry Cachina b , Mine Kucur c , Altay Gezer d , Riza Madazli d , Osman Ozdemir a and Xavier Norel b Objective Preeclampsia is characterized by hypertension and proteinuria developing after 20 weeks of gestation. Increased vasoconstriction can be one of the major underlying pathophysiological event in this syndrome. We examined the role of vasoconstrictor prostanoid, prostaglandin F 2a (PGF 2a ) in preeclamptic and normotensive human umbilical veins. Methods Umbilical veins were set up in organ bath. The concentration-response curves of PGF 2a (endogenous agonist of prostaglandin F receptor) and fluprostenol (prostaglandin F receptor selective agonist) were determined in normal and preeclamptic veins either in the absence or presence of BAY u3405 (thromboxane A 2 receptor selective antagonist). PGF 2a and its major metabolite concentrations were measured by enzyme immunoassay kit. The expression of vasoconstrictor prostanoid receptors was determined by western blot. Results The concentration-dependent contractions to PGF 2a and fluprostenol were significantly increased in umbilical vein preparations derived from preeclamptic women compared with those of normotensives. Increased reactivity was related with enhanced sensitivity to these spasmogens in preeclamptic veins. BAY u3405 (10 mmol/l) did not modify the responsiveness to PGF 2a in normal umbilical veins whereas moderately reduced the contractions in preeclamptic preparations. Serum concentrations of PGF 2a and its major metabolite, 13,14- dihydro-15-keto-PGF 2a, were comparable between preeclamptics and normotensives whereas the metabolite concentration was elevated in umbilical cord serum of preeclamptics. 13,14-dihydro-15-keto-PGF 2a, release was also increased in umbilical vein preparations of preeclamptic women. An increased prostaglandin F receptor protein expression was determined whereas EP3 and thromboxane A 2 protein expressions were unchanged in preeclamptic umbilical veins. Conclusion Prostaglandin F and thromboxane A 2 receptors activation by PGF 2a could be involved in umbilical vasospasm observed in preeclampsia. J Hypertens 28:000– 000 Q 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. Journal of Hypertension 2010, 28:000–000 Keywords: EP3 receptor, prostaglandin F-receptor, human umbilical vein, preeclampsia, prostaglandin F 2a , thromboxane A 2 receptor, vasoconstriction Abbreviations: E max , maximal contraction; HUA, human umbilical artery; HUV, human umbilical vein; IUGR, intrauterine growth-restriction; PAGE, polyacrylamide gel; PG, prostaglandin; 5-HT, serotonin; TXA 2 , thromboxane A 2 a Istanbul University, Faculty of Pharmacy, Department of Pharmacology, Istanbul, Turkey, b INSERM U698: Haemostasis, Bio-engineering and Cardiovascular Remodeling, CHU X, Bichat, Paris, France, c Fikret Biyal Central Biochemistry Laboratory and d Department of Obstetrics and Gynecology, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey Correspondence to Gokce Topal, PhD, Istanbul University, Faculty of Pharmacy, Department of Pharmacology, 34116, Beyazit, Istanbul, Turkey Tel: +90 212 527 18 25; fax: +90 212 527 18 25; e-mail: gokce_topal@hotmail.com Received 5 February 2010 Revised 15 July 2010 Accepted 20 July 2010 Introduction Preeclampsia is one of the leading causes of maternal and perinatal morbidity as well as mortality. This pathology is associated with as an elevation in maternal blood pressure (systolic 140 mmHg and diastolic 90 mmHg) and pro- teinuria (300 mg in 24 h) developing after 20 weeks of gestation. Although, the etiology of preeclampsia is not fully understood, increased vasoconstriction in maternal arteries as well as in umbilical vessels is one of the major underlying pathophysiological events in this syndrome [1,2]. Human umbilical vessels lack autonomic innervation and hence the regulation of vascular tone depends on circu- lating as well as locally released substances in the blood stream. The human umbilical vein (HUV) carries oxyge- nated blood from the placenta to the growing fetus. The reduction in blood flow owing to the increased vascular tone may result in retarded fetal growth and low birth weight [3,4]. Locally released arachidonic acid metabolites derived from cyclooxygenase activity are known to alter several physiological events. For example, prostaglandin F 2a , regulates a number of key functions in female reproduc- tion, such as, luteolysis, ovarian function and luteal main- tenance of pregnancy. Prostaglandin F 2a (PGF 2a ) and the metabolite 13,14-dihydro-15-keto-PGF 2a have also been implicated in smooth muscle contraction via prostaglandin F receptors and exert a significant uterotonic activity Original article 1 0263-6352 ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/HJH.0b013e32833e868f