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Vascular endothelial growth factor (VEGF) has been implicated in the regulation of vesicular transport of amniotic fluid via caveolae across the amnion. This study tested the hypothesis that VEGF regulates caveolar function by stimulating caveolin-1 expression and phosphorylation in ovine amniotic epithelial cells (oAECs). Using primary cultures of oAECs, caveolin-1 was identified by immunofluorescent staining. Caveolin-1 messenger RNA (mRNA) abundance was determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and protein by Western blotting. The effects of VEGF( 165) on caveolin-1 expression and phosphorylation were determined. Caveolin-1 immunoreactivity was detected in oAECs. In response to 10 ng/mL VEGF( 165), caveolin-1 mRNA levels increased whereas the protein levels were unaffected. Furthermore, VEGF stimulated caveolin-1 phosphorylation, an effect abrogated by the inhibition of c-Src protein kinase. These data suggest that VEGF upregulates caveolin-1 activity through c-Src signaling pathways. Our observations support the hypothesis that VEGF regulates amniotic fluid transport across the amnion by stimulating caveolin-1 activity to mediate caveolar function in amnion cells.

A study of the effects of endothelin on fetal cardiovascular and urinary functions in continuously catheterized ovine fetuses reveals that endothelin infusion leads to increased plasma atrial natriuretic factor (ANF) accumulation. The elevated plasma ANF release is either due to the direct action of endothelin on fetal atrial cardiocytes or due to cardiovascular and endocrine changes following endothelin infusion. The vasoconstrictive action of endothelin on umbilical vessels results in hemodynamic effects such as hypoxia that contribute to increased plasma ANF concentrations. Endothelin increases fetal urine flow responses by inducing systemic hypertension.

A study is conducted to examine whether cardiovascular, endocrine and fluid reactions to exogenous atrial natriuretic factor (ANF) are changed by the fetal automatic nervous system. The results indicate that the autonomic nervous system may be involved in changing fetal arterial pressure, heart rate, blood volume, plasma arginine vasopressin (AVP) and urine flow responses to ANF. Multiple responses to ANF in the late-gestation ovine fetus are considerably modulated by the autonomic nervous system.

Long-term loss of fetal blood can occur with fetomaternal hemorrhage, vasoprevia, or placental previa. Our objective was to determine the effects of progressive fetal blood loss over 10 days on fetal plasma erythropoietin (EPO) concentration and its relationship to arterial [PO.sub.2], hematocrit, and the volume of blood loss. Late-gestation fetal sheep (n = 8) were hemorrhaged daily at a rate of 1 ml/min over 10 days. The extent of hemorrhage differed in each fetus and ranged from 30 to 80 ml/day, with the cumulative volume removed ranging from 78 to 236 mi/kg estimated fetal weight. Four fetuses served as time controls. EPO concentration measurements were by radioimmunoassay. Statistical analyses included regression, correlation, and analysis of variance. We found that EPO and arterial [PO.sub.2] were unchanged until the cumulative hemorrhage volume exceeded 20-40 ml/kg. Once this threshold was exceeded, plasma EPO concentration increased progressively throughout the study and averaged 14.3 [+ or -] 3.2 times basal values on day 10. EPO concentration, arterial [PO.sub.2], and hematocrit changes were related curvilin-early to cumulative hemorrhage volume (P [is less than] 0.01), whereas the relationship between plasma EPO and arterial [PO.sub.2] was log linear (P [is less than] 0.001). We conclude that 1) fetal plasma EPO concentration and arterial [PO.sub.2] are insensitive to a slow, mild-to-moderate blood loss over several days; 2) unlike the rapid return of EPO to normal within 48 h after acute hemorrhage, fetal EPO concentration undergoes a progressive increase with moderate-to-severe blood loss over several days; 3) the long-term hemorrhage-induced changes in EPO are best correlated with arterial [PO.sub.2]; and 4) the fetal EPO response to hemorrhage does not appear to be limited by the fetus's ability to produce EPO. hemorrhage; fetal hypoxia; oxygen tension; sheep