Endothelial cells regulate proximal tubule epithelial cell sodium transport

Background. Proximal tubule epithelial cells are in close contact with the renal microvasculature, but the effect of endothelial cells (ECs) on proximal tubule epithelial cell (PTEC) function is not known. Methods. To determine if ECs regulate PTECs, we coincubated ECs with PTECs in a system that permitted cross-talk between the two cell types and the vectorial transport of sodium. Results. In the presence (but not absence) of ECs, adding bradykinin or acetylcholine increased cGMP and decreased sodium transport, as well as Na,K-ATPase in PTECs. Interleukin (IL)(1B) preconditioning of ECs also increased cGMP and decreased sodium transport and Na,K-ATPase in PTECs. Bradykinin, acetylcholine, and Ids EC-dependent effects were reversed with the nitric oxide (NO) synthase inhibitor L-NNA. In the absence of ECs, the addition of NO donors to PTECs increased cGMP and decreased sodium transport and Na,K-ATPase. 8Br-cGMP also decreased PTEC sodium transport and Na,K-ATPase. Conclusion. Endothelial cells regulate PTEC function. This effect is mediated by NO synthase-dependent up-regulation of cGMP in PTECs.