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 IL1B 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.


CONCLUSIONS
Endothelial cells regulate PTEC function. This effect is mediated by NO synthase-dependent up-regulation of cGMP in PTECs.
Linas
S L
SL
Denver Health Medical Center, University of Colorado Health Sciences Center, USA. STUART.LINAS@UCHSC.EDU
Repine
J E
JE
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D001920:Bradykinin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D018920:Coculture Techniques; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D000109:Acetylcholine; D001920:Bradykinin