Angiotensin II modulates ion transport in rat proximal tubules through CYPmetabolites

To assess the effect of angiotensin II on ion transport in rat isolated pro ximal tubules and establish the arachidonic acid cytochrome P450 metabolite s' role mediating angiotensin II effect and to analyze whether corticostero ids play a role modulating this effect, we studied the effect of low (10 an d 100 pM) and high (0.1-1 mu M) angiotensin II concentrations on proximal t ubule ion transport, measured as Rb-86 uptake. Low angiotensin II produced a stimulation on the Rb-86 uptake (195.79 +/- 35, 377.9 +/- 81, and 300 +/- 49 pg Rb-86/mu g protein/2 min, for control and 10 and 100 pM angiotensin II, respectively). High angiotensin II concentration inhibited ion transpor t (0.1 mu M, 57.9 +/- 5 and 1 mu M, 47.3 +/- 4 pg Rb-86/mu g protein/2 min) , this effect was prevented by 17-ODYA and by losartan, while indomethacin had no effect. Dexamethasone treatment increased angiotensin II-induced Rb- 86 uptake inhibition and arachidonic acid metabolism (19-, 20-HETE and 12-H ETE), while adrenalectomy partly prevented angiotensin II-induced inhibitio n and decreased cytochrome P450-dependent arachidonic acid metabolism. In c onclusion, high doses of angiotensin II produce inhibition of ion transport in rat isolated proximal tubules; this effect is mediated by AT(1) recepto rs, involves cytochrome P450-dependent arachidonic acid metabolites, and is upregulated by corticosteroids. (C) 2000 Academic Press.