Angiotensin II modulates ion transport in rat proximal tubules through CVP metabolites

To assess the effect of angiotensin II on ion transport in rat isolated proximal tubules and establish the arachidonic acid cytochrome P450 metabolites' role mediating angiotensin II effect and to analyze whether corticosteroids play a role modulating this effect, we studied the effect of low (10 and 100 pM) and high (0.1-1 μM) angiotensin II concentrations on proximal tubule ion transport, measured as ⁸⁶Rb uptake. Low angiotensin II produced a stimulation on the ⁸⁶Rb uptake (195.79 ± 35, 377.9 ± 81, and 300 ± 49 pg ⁸⁶Rb/μg protein/2 min, for control and 10 and 100 pM angiotensin II, respectively). High angiotensin II concentration inhibited ion transport (0.1 μM, 57.9 ± 5 and 1 μM, 47.3 ± 4 pg ⁸⁶Rb/μg protein/2 min), this effect was prevented by 17-ODYA and by losartan, while indomethacin had no effect. Dexamethasone treatment increased angiotensin II-induced ⁸⁶Rb uptake inhibition and arachidonic acid metabolism (19-, 20-HETE and 12-HETE), while adrenalectomy partly prevented angiotensin II-induced inhibition and decreased cytochrome P450-dependent arachidonic acid metabolism. In conclusion, high doses of angiotensin II produce inhibition of ion transport in rat isolated proximal tubules; this effect is mediated by AT₁ receptors, involves cytochrome P450-dependent arachidonic acid metabolites, and is upregulated by corticosteroids. (C) 2000 Academic Press.