Extracellular ATP induces albuminuria in pregnant rats

Background. As circulating plasma ATP concentrations are increased in pre-eclampsia, we tested whether increased plasma ATP is able to induce albuminuria during pregnancy. Methods. Pregnant (day 14) and non-pregnant rats were infused with ATP (3000 µg/kg bw) via a permanent jugular vein cannula. Albuminuria was determined, and blood samples were taken for leukocyte counts, plasma ATP and plasma haemopexin activity. At Day 20 of pregnancy, rats were sacrificed, fetuses and placentas weighed and kidney and placental tissue were snap frozen for immunohistology. Results. ATP infusion induced albuminuria exclusively in pregnant rats, together with increased neutrophil counts, decreased staining for glomerular sialoglycoproteins and CD39 expression, significant intraglomerular monocyte infiltration and increased glomerular intracellular adhesion molecule-1 (ICAM-1) expression. Plasma haemopexin activity was increased in saline-infused pregnant rats as compared to non-pregnant rats but was inhibited in pregnant ATP-infused rats (to non-pregnant levels). At the end of pregnancy (Day 20), increased plasma ATP levelwas exclusively seen in ATP-infused pregnant rats. In pregnant rats as compared with non-pregnant rats, we found decreased expression of glomerular AT-1 receptors, which was increased after ATP infusion exclusively in pregnant animals. Conclusion. The present study shows that ATP infusion induced a pro-inflammatory response leading to glomerular albuminuria exclusively in the pregnant rat. Why extracellular ATP showed this pro-inflammatory response exclusively in the pregnant condition is unclear but is probably related with relatively enhanced non-specific immunity and inflammatory reactions characteristic for the pregnant condition.