The mineralocorticoid receptor and oxidative stress.
Reactive oxygen species are profoundly important for many physiologic functions and are also pivotal to numerous disease processes, particularly those involving inflammation. Much evidence has accrued demonstrating that aldosterone acts locally in many cells aside from those in the cortical collecting duct. Peripheral blood monocytes and vascular smooth muscle cells are both influenced by aldosterone to produce reactive oxygen species. This production contributes to nuclear factor kappaB (NF-kappaB) activation and the genes regulated by this transcription factor. Aldosterone thereby plays an important role in atherosclerosis and hypertension-induced vascular injury. Aldosterone interacts with angiotensin (Ang) II-induced signaling. Both aldosterone and Ang II initiate ERK1/2 and JNK signaling; the effects of the two compounds is additive and involves the epidermal growth factor receptor. Recent data suggest that reactive oxygen species, might contribute to aldosterone production in nonadrenal tissues. A novel oxidized derivative of linoleic acid is a prime candidate in this regard. Oxidative stress may impair mineralocorticoid receptor function by inhibiting aldosterone binding. The latter finding has particularly important implications for elderly persons who exhibit increased oxidative stress and who are at risk for diminished aldosterone function in the distal nephron and subsequent hyperkalemia.
Fiebeler
Anette
A
Medical Faculty of the Charité, Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, HELIOS Klinikum-Berlin, Germany.
Luft
Friedrich C
FC
D000450:Aldosterone / Q000502:physiology*; D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species; D018161:Receptors, Mineralocorticoid / Q000502:physiology*
D017382:Reactive Oxygen Species; D018161:Receptors, Mineralocorticoid; D000804:Angiotensin II; D000450:Aldosterone