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Neurokinin B Is a Paracrine Vasodilator in the Human Fetal Placental Circulation

Academic Unit of Child Health (P.B., C.P.S.), University of Manchester, St. Mary’s Hospital, Manchester M13 0JH, United Kingdom; and School of Animal and Microbial Sciences (N.J.B., R.J.W., P.J.L., N.M.P.), University of Reading, Reading RG6 6AJ, United Kingdom

Address all correspondence and requests for reprints to: Paul Brownbill, Academic Unit of Child Health, University of Manchester, St. Mary’s Hospital, Hathersage Road, Manchester M13 0JH, United Kingdom. E-mail: paul.brownbill{at}man.ac.uk.

Neurokinin (NK) B is a member of the tachykinin family of neurotransmitters, exerting hypotensive or hypertensive effects in the mammalian vasculature through synaptic release from peripheral neurons, according to either NK₁ and NK₂ or NK₃ receptor subtype expression, respectively. There is recent evidence that NKB is expressed by the syncytiotrophoblast of the human placenta, an organ that is not innervated. We hypothesized that NKB is a paracrine modulator of tone in the fetal placental circulation. We tested this hypothesis using the in vitro perfused human placental cotyledon. Our data show that NKB is a dilator of the fetal vasculature, causing a maximal 25.1 ± 4.5% (mean ± SEM; n = 5) decrease in fetal-side arterial hydrostatic pressure (5-µM NKB bolus; effective concentration in the circulation, 1.89 nM) after preconstriction with U-46619. RT-PCR demonstrated the presence of mRNA for NK₁ and NK₂ tachykinin receptors in the placenta. Using selective receptor antagonists, we found that NKB-induced vasodilation is through the NK₁ receptor subtype. We found no evidence for the involvement of either nitric oxide or prostacyclin in this response. This study demonstrates a paracrine role for NKB in the regulation of fetal placental vascular tone.

This work was supported by an Action Research Endowment Fund (Manchester group funding) and an Medical Research Council program grant (Reading group funding). N.J.B. holds a Society for Endocrinology Prize studentship.

Abbreviations: FAHP, Fetal arterial hydrostatic pressure; FMAHP, fetal and MAHP; HUVEC, human umbilical vein endothelial cell; L-NAME, nitro-L-arginine methyl ester hydrochloride; MAHP, maternal arterial hydrostatic pressure; NK, neurokinin; NO, nitric oxide.

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