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Romena Qazi1 , Ian M Bird1 , Ronald R Magness1 2 *, Jing Zheng1
Department of Obstetrics & Gynecology, Perinatal Research Laboratories, Meriter Hospital, Madison, WI 1
Department of Animal Sciences, University of Wisconsin- Madison, Madison, WI 2
During ovine pregnancy fetal placental blood flow is dramatically elevated in association with increases in placental bFGF, VEGF, and NO production as well as eNOS expression. We recently reported that both bFGF and VEGF increase OFPAE cell proliferation, activate the Mitogen Activated Protein Kinase (MAPK) signaling pathway, and that bFGF stimulates eNOS expression (Zheng et al, Endo 140:1399-1407,1999). In bovine coronary endothelial cells, VEGF-induced mitogenesis was reported to be mediated via the NO/MAPK pathway. We therefore tested the hypothesis that bFGF and VEGF stimulated OFPAE cell proliferation is modulated by NO via the MAPK signaling pathway. We observed that: 1) bFGF and VEGF increased (p<0.05) OFPAE cell proliferation in a dose dependent fashion (0.001-100ng/ml) with maximum responses at 1-10ng/ml of 1.0-2.0 fold of control; 2) 10 ng/ml bFGF and VEGF elevated (p<0.05) NO production in a time dependent fashion with a maximal effect of 1.5- and 3.5-fold, respectively at 24h; 3) OFPAE cell proliferation with bFGF and VEGF (10 ng/ml) was dose dependently reduced (maximum 80-100%) by the specific MAPK kinase inhibitor PD 98059 (1-100uM) and also by two NO synthase inhibitors (L-NMMA or L-NAME; 0.01uM-1mM); and 4) L-NMMA (100uM) inhibited bFGF and VEGF-induced increases in MAPK phosphorylation by 30-50%. We conclude that NO partially modulates bFGF and VEGF stimulated OFPAE cell proliferation via the MAPK signaling pathway. Thus angiogenic factor induced increases in NO may contribute to the rise in placental angiogenesis and blood flow during ovine pregnancy. (Supported by NIH grants HL49210, HD33255, HL57653, HL56702).
This abstract is being presented on Tuesday, August 3 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.