AT1 receptor and NAD(P)H oxidase mediate angiotensin II-stimulated antioxidant enzymes and mitogen-activated protein kinase activity in the rat hypothalamus

Abstract

Introduction. Angiotensin II (AngII) regulates blood pressure and water and electrolyte metabolism through the stimulation of NAD(P)H oxidase and production of reactive oxygen species (ROS) such as O 2 -, which is metabolised by superoxide dismutase, catalase and glutathione peroxidase. We assessed the role of AT 1 and AT 2 receptors, NAD(P)H oxidase and protein kinase C (PKC) in Ang II-induced sodium and water excretion and their capacity to stimulate antioxidant enzymes in the rat hypothalamus, a brain structure known to express a high density of AngII receptors. Materials and methods. Male Sprague-Dawley rats were intracerebroventricularly (ICV) injected with AngII and urinary sodium and water excretion was assessed. Urine sodium concentration was determined using flame photometry. After decapitation the hypothalamus was microdissected under stereomicroscopic control. Superoxide dismutase, catalase and glutathione peroxidase activity were determined spectrophotometrically and extracellular signal-regulated kinase (ERK1/2) activation was analysed by Western blot. Results. AngII-ICV resulted in antidiuresis and natriuresis. ICV administration of losartan, PD123319, apocynin and chelerythrine blunted natriuresis. In hypothalamus, AngII increased catalase, superoxide dismutase and glutation peroxidase activity and ERK1/2 phosphorylation. These actions were prevented by losartan, apocynin and chelerythrine, and increased by PD123319. Conclusions. AT 1 and AT 2 receptors, NAD(P)H oxidase and PKC pathway are involved in the regulation of hydromineral metabolism and antioxidant enzyme activity induced by AngII.

Development of Angiotensin II-induced Abdominal Aortic Aneurysms Is Independent of Catalase in Mice

“…Therefore, it is likely that AngII infusion increases catalase activity possibly through compensated mechanisms against injury. Indeed, Silva et al 34 have demonstrated the effect of AngII on catalase activity in rat hypothalamus. In agreement with the former report, we found that AngII infusion into mice augmented catalase activity in the aorta of wild-type mice.…”

Angiotensin II and its receptor in activated microglia enhanced neuronal loss and cognitive impairment following pilocarpine-induced status epilepticus

“…Losartan or minocycline was administered intracerebroventricularly (i.c.v.) at doses of 100 μg/5 μl 1 h before the injections of lithium chloride (Silva et al, 2010;Michels et al, 2014). For long-term survival studies (12-21 days), losartan was administered everyday as described above until every animal was killed.…”

Adrenomedullin and Angiotensin II in Rat Cerebellar Vermis: Reactive Oxygen Species Production

“…These data indicate that redox signaling, NAD(P) H-oxidase-dependent production of superoxide are involved in ANG II-induced stimulatory actions in cerebellar neurons, which explains the increases of antioxidant enzyme activity such as CAT, SOD and GPx. It is well established in peripheral tissues and in brain that NAD(P)H oxidase is regulated by PKC, an enzyme which is known to be activated by ANG II [22,48]. In fact, pre-incubation of hypothalamic tissue with the PKC inhibitor, chelerythrine, completely attenuated ANG II-stimulated antioxidant enzyme activity of CAT, SOD and GPx in vitro [48].…”

“…It is well established in peripheral tissues and in brain that NAD(P)H oxidase is regulated by PKC, an enzyme which is known to be activated by ANG II [22,48]. In fact, pre-incubation of hypothalamic tissue with the PKC inhibitor, chelerythrine, completely attenuated ANG II-stimulated antioxidant enzyme activity of CAT, SOD and GPx in vitro [48]. The possible role of PKC, NAD(P)H oxidase and antioxidant enzyme activation in ANG II signaling in cerebellum was shown by Figueira and Israel [15] since they demonstrated that the PKC inhibitor, chelerythrine, completely blocked ANG II-induced antioxidant enzyme activity of CAT, SOD and GPx in vitro.…”