Cardiovascular Pharmacology Role of monoamine oxidases in the exaggerated 5-hydroxytryptamine-induced tension development of human isolated preeclamptic umbilical artery Sai Wang Seto a , Ho Yeung Lam a , Wing Sze Lau a , Alice L.S. Au a , Tsz Yan Lam a , Stephen S.C. Chim b , Sai Ming Ngai c , Shun Wan Chan d , Tak Yeung Leung b , John H.K. Yeung a , Siu Kai Kong e , George P.H. Leung f , Simon M.Y. Lee g , Yiu Wa Kwan a,h,i, ⁎ a Department of Pharmacology, The Chinese University of Hong Kong, Hong Kong, PR China b Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, PR China c Department of Biology, The Chinese University of Hong Kong, Hong Kong, PR China d State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China e Biochemistry, Faculty of Science, The Chinese University of Hong Kong, Hong Kong, PR China f Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong Kong, PR China g Institute of Chinese Medical Sciences, University of Macau, Av. Padre Tomas Pereira S.J., Taipa, Macau, PR China h Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, PR China i Institute of Vascular Medicine, The Chinese University of Hong Kong, Hong Kong, PR China abstract article info Article history: Received 11 November 2008 Received in revised form 3 December 2008 Accepted 18 December 2008 Available online 19 January 2009 Keywords: Monoamine oxidase Preeclampsia Umbilical artery 5-hydroxytryptamine We investigated the role(s) of monoamine oxidases (MAOs) on the altered 5-hydroxytryptamine (5-HT, serotonin)-induced tension development of the isolated umbilical artery of preeclamptic pregnancy of Chinese women. An enhanced 5-HT-induced tension development of the umbilical artery of preeclamptic pregnancy was observed when compared with that of normal pregnancy. The enhanced component of 5-HT- induced tension development was eradicated by clorgyline (a MAO-A inhibitor). Blockade of eNOS (endothelial isoform nitric oxide synthase) (N ω -nitro-L-arginine methyl ester), 5-HT transporter (citalopram), 5-HT receptor subtypes (5HT 2B , SB 204741; 5-HT 2C , RS 102221; 5-HT 7 , SB 269970), and endothelium denudation of the umbilical artery of normal pregnancy mimicked the enhanced 5-HT-induced tension development as observed in the preeclamptic tissues. In contrast, no apparent changes in 5-HT-induced tension development of the umbilical artery of preeclamptic pregnancy were observed with the same pharmacological manipulations. A decreased protein expression levels of MAO-A and eNOS (no iNOS and MAO-B expression was detected) and no change in caveolin-1 and 5-HT transporter expression were demonstrated in the umbilical artery (endothelium intact) lysate of preeclamptic pregnancy, compared to that of the umbilical artery of normal pregnancy. Thus, in the umbilical artery of preeclamptic pregnancy, a decrease of MAO-A and eNOS protein expression levels are probably associated with, or responsible for, the exaggerated 5-HT-induced tension development. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Preeclampsia is a serious condition in which an elevated blood pressure and other disturbances (proteinuria and oedema) develop in the second-half period of pregnancy. Preeclampsia affects approxi- mately 5–8% of all pregnancies over 20 weeks (Dekkar and Sibai, 1998). Women with a history of preeclampsia are at an increased risk of cardiovascular diseases development (Irgens et al., 2001; Magnus- sen et al., 2007; Smith et al., 2001; Ray et al., 2005) suggesting that preeclampsia and cardiovascular diseases may share common causes (Rodie et al., 2004; Sattar et al., 1997). 5-Hydroxytryptamine (5-HT) is a potent vasoconstrictor (Karlsson et al., 1999) of human isolated placental vessels (Gujrati et al., 1996) and umbilical arteries (Gupta et al., 2006). In preeclamptic women, an elevated level of 5-HT in plasma and the maternal circulation was detected (Gonzalez et al., 1993), and the preeclampsia-related hypertension can be controlled by ketanserin (a 5-HT receptor antagonist) (Bolte et al., 2001; Weiner et al., 1984). Hence, these observations strongly suggest that 5-HT plays an important role in the development/progression of preeclampsia. In contrast to the observa- tion of an enhanced 5-HT-induced contraction of the umbilical artery of preeclamptic pregnancy (Bertrand and St. Louis, 1999; Bodelsson et al., 1995), Gupta et al. (2006) failed to demonstrate a difference in European Journal of Pharmacology 605 (2009) 129–137 ⁎ Corresponding author. Room 409B, Department of Pharmacology, Basic Medical Sciences Building, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong. Tel.: +852 2609 6884; fax: +852 2603 5139. E-mail address: yiuwakwan@cuhk.edu.hk (Y.W. Kwan). 0014-2999/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2008.12.054 Contents lists available at ScienceDirect European Journal of Pharmacology journal homepage: www.elsevier.com/locate/ejphar