Nitric oxide production by decidual endothelial cells is not reduced in preeclampsia.
OBJECTIVE
To investigate whether decidual endothelial cells (DEC) contribute to the pathogenesis of preeclampsia through abnormal nitric oxide production. Decidual endothelial cells from normal (NDEC) and preeclamptic (PEDEC) pregnancies, and also human umbilical vein endothelial cells (HUVEC), were examined.


METHODS
HUVEC, NDEC, and PEDEC were incubated for 45 min in serum-free media with the addition of potential stimulators [calcium ionophore (A23187), sepiapterin, and a combination of cytokines (TNF-alpha, gamma-IFN and LPS)], and the competitive inhibitor, NG-monomethyl-L-arginine (L-NMMA). These were added alone or in combination. Supernatants were measured for nitrate/nitrite (NOx) levels and the cells acid-extracted for measurement of cyclic guanosine monophosphate (cGMP). The effect of 30 min of shear stress (approximately 20 dynes/cm2) on NO and cGMP production by NDEC and PEDEC and on production of prostacyclin and thromboxane A2, was assessed.


RESULTS
PEDEC and HUVEC both produced more NO than NDEC under all conditions examined. Cell-associated cGMP levels, however, were not different among the cell groups but were increased by A23187 and inhibited by L-NMMA. In control conditions, shear stress stimulated cGMP levels 5-fold (p<0.01) in both NDEC and PEDEC, and PGI2 production 2-fold (p<0.05).


CONCLUSIONS
DEC from preeclamptic women do not have reduced NO production and respond normally to shear stress by increasing cGMP and PGI2 production. Our results are consistent with other reports of equal or higher NO levels in preeclampsia and indicate that reduced NO production by endothelial cells is not the explanation for the vasoconstriction of uterine vessels.
Rowe
Janet
J
Renal and Reproductive Group, University of Sydney at Royal North Shore Hospital, St. Leonards, NSW, Australia.
Campbell
Suzanne
S
Gallery
Eileen D M
ED
D000328:Adult; D000001:Calcimycin; D016022:Case-Control Studies; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis*; D016207:Cytokines; D003656:Decidua / Q000166:cytology; D004730:Endothelium, Vascular / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011621:Pteridines; D011622:Pterins; D013928:Thromboxane A2 / Q000096:biosynthesis; D014471:Umbilical Veins / Q000166:cytology; D019323:omega-N-Methylarginine
D016207:Cytokines; D011621:Pteridines; D011622:Pterins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000001:Calcimycin; D013928:Thromboxane A2; C016727:sepiapterin; D011464:Epoprostenol; D006152:Cyclic GMP