Control of proximal tubule acidification by the endothelium of the peritubular capillaries

Guanosine 3',5'-cyclic monophosphate (cGMP), a nitric oxide mediator, stimulates Na+/H+ exchange in brush-border vesicles of the renal cortex. The aim of the present work was to test whether the endothelium of the peritubular capillaries modulated the rate of proximal luminal acidification through the release of endothelium-derived nitric oxide (EDNO). Perfusion of the tubule lumen with dibutyryl cGMP increased net proton flux (J(H)). Two agents that elicit EDNO production, bradykinin (BK) and carbamylcholine (Cch), increased J(H) when added to the peritubular capillary perfusate. Bradykinin did not affect J(H) when the peritubular capillaries and the lumen were perfused with Na-free solution. Methylene blue (MB) and N-G-nitro-L-arginine methyl ester (L-NAME) blocked the elevation in J(H) by Cch and also decreased basal J(H) Bradykinin increased cGMP content of isolated proximal convoluted tubules, but only if they were coincubated with endothelial cells. This effect of BK was blocked by L-NAME. The results suggest that the endothelium of the peritubular capillaries affects proximal tubule acidification through changes of cGMP in proximal tubule cells, probably via stimulation of Na+/H+ exchanger.