NOS EXPRESSION IS INCREASED IN ENDOTHELIAL-CELLS EXPOSED TO PLASMA FROM WOMEN WITH PREECLAMPSIA

Endothelial cell function is proposed to be altered by a factor(s) in the maternal circulation of women with the pregnancy disorder preeclam psia. Our initial hypothesis was that in preeclampsia, such factor(s) would reduce synthesis of nitric oxide (NO) by endothelial cells. Howe ver, we previously observed increased NO synthase activity in endothel ial cells exposed to plasma from preeclamptic women. This study tested whether exposing cells to plasma from preeclamptic women increased tr anscription and/or translation of endothelial NO synthase. Cultured bo vine coronary microvascular endothelial cells were exposed to 2% plasm a from patients with preeclampsia and patients with uncomplicated preg nancies. Nitrite production was greater in endothelial cells exposed t o plasma from preeclamptic women (8.97 +/- 0.54 vs. 6.39 +/- 0.59 nmol nitrites . 10(6) cells(-1). 24 h(-1); P < 0.05). Similarly, endotheli al NO synthase mass as measured by Western immunoblotting was signific antly increased (20,980 +/- 1,406 vs. 15,047 +/- 1,003 absorbancy unit s; P < 0.02). There was no detectable difference in mRNA for endotheli al NO synthase. However, actinomycin (3 mu g/ml), a transcription inhi bitor, significantly decreased nitrite production only in cells expose d to plasma from preeclamptic women (5.28 +/- 0.52 vs. 3.56 +/- 0.36 n mol . 10(6) cells(-1). 24 h(-1), P < 0.05). These findings indicate a regulation of the ''constitutive'' isoform of NO synthase by factor(s) in the blood of preeclamptic women, which may have significance in th is pathological condition of pregnancy.