Angiotensin II modulates ion transport in rat proximal tubules through CYP 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 microM) angiotensin II concentrations on proximal tubule ion transport, measured as (86)Rb uptake. Low angiotensin II produced a stimulation on the (86)Rb uptake (195.79 +/- 35, 377.9 +/- 81, and 300 +/- 49 pg (86)Rb/microg protein/2 min, for control and 10 and 100 pM angiotensin II, respectively). High angiotensin II concentration inhibited ion transport (0.1 microM, 57.9 +/- 5 and 1 microM, 47.3 +/- 4 pg (86)Rb/microg protein/2 min), this effect was prevented by 17-ODYA and by losartan, while indomethacin had no effect. Dexamethasone treatment increased angiotensin II-induced (86)Rb 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 AT(1) receptors, involves cytochrome P450-dependent arachidonic acid metabolites, and is upregulated by corticosteroids.
Sánchez-Mendoza
A
A
Department of Pharmacology, Instituto Nacional de Cardiología "Ignacio Chávez,", 14080, México DF.
López-Sánchez
P
P
Vázquez-Cruz
B
B
Rios
A
A
Martínez-Ayala
S
S
Escalante
B
B
D000315:Adrenalectomy; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012414:Rubidium Radioisotopes / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D012414:Rubidium Radioisotopes; D000804:Angiotensin II; D016718:Arachidonic Acid; C047008:17-octadecynoic acid; D010042:Ouabain; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D019808:Losartan; D007213:Indomethacin