Role of monoamine oxidases in the exaggerated 5-hydroxytryptamine-induced tension development of human isolated preeclamptic umbilical artery.
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(omega)-nitro-L-arginine methyl ester), 5-HT transporter (citalopram), 5-HT receptor subtypes (5HT2B, SB 204741; 5-HT2C, RS 102221; 5-HT7, 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.
Seto
Sai Wang
SW
Department of Pharmacology, The Chinese University of Hong Kong, Hong Kong, PR China.
Lam
Ho Yeung
HY
Lau
Wing Sze
WS
Au
Alice L S
AL
Lam
Tsz Yan
TY
Chim
Stephen S C
SS
Ngai
Sai Ming
SM
Chan
Shun Wan
SW
Leung
Tak Yeung
TY
Yeung
John H K
JH
Kong
Siu Kai
SK
Leung
George P H
GP
Lee
Simon M Y
SM
Kwan
Yiu Wa
YW
D000328:Adult; D051242:Caveolin 1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007537:Isometric Contraction; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000008:administration & dosage* / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D014469:Umbilical Arteries / Q000378:metabolism; D055815:Young Adult
D051242:Caveolin 1; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D052250:Nitric Oxide Synthase Type III; D008995:Monoamine Oxidase