Preeclampsia is associated with loss of neuronal nitric oxide synthase expression in vascular smooth muscle cells of the human umbilical cord.
OBJECTIVE
Umbilical blood vessels are not innervated and regulation of blood flow to the placenta must depend on structural changes and the effect of vasoactive factors. Failure to achieve these adaptations may result in reduced fetoplacental perfusion. The purpose of this study was to determine whether neuronal nitric oxide synthase (nNOS) is expressed in human vascular smooth muscle cells (VSMCs) of the fetoplacental circulation. nNOS has been described as a non-endothelial NOS counterregulating vasoconstriction only in the VSMCs of animal models. Therefore, we investigated nNOS expression in the fetoplacental unit from preeclamptic and healthy pregnancies.


RESULTS
We investigated nNOS regulation by immunohistochemistry, Western blotting and reverse transcriptase-polymerase chain reaction analysis. nNOS activity was determined by measuring the conversion of L-3H-arginine to L-3H-citrulline. nNOS expression was revealed only in VSMCs of the human umbilical veins, but not in umbilical arteries. A more direct assessment of nNOS activity showed that a small, but consistent amount of nNOS is present in the denuded media of the umbilical vein. In VSMCs of the umbilical veins during preeclampsia a total loss of nNOS protein expression and a significant decrease in mRNA expression were seen.


CONCLUSIONS
Loss of nNOS expression is associated with preeclampsia. It may alter the regulation of blood flow in the fetal and maternal placental vasculature in preeclampsia. However, the impact of NO produced by nNOS on the vascular tone of umbilical veins remains to be elucidated.
Schönfelder
G
G
Institute of Clinical Pharmacology and Toxicology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany. schoenfe@zedat.fu-berlin.de
Fuhr
N
N
Hadzidiakos
D
D
John
M
M
Hopp
H
H
Paul
M
M
D000328:Adult; D015153:Blotting, Western; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D032389:Myocytes, Smooth Muscle / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014469:Umbilical Arteries / Q000201:enzymology*; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism; D014471:Umbilical Veins / Q000201:enzymology*
D017931:DNA Primers; D012333:RNA, Messenger; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I