Aims Activation of the renin–angiotensin system (RAS), renal oxidative stress and inflammation are constantly present in experimental hypertension. Nitric oxide (NO) inhibition with Nw-nitro-L-arginine methyl ester (L-NAME) has previously been reported to produce hypertension, increased expression of Angiotensin II (Ang II) and renal dysfunction. The use of Losartan, an Ang II type 1 receptor (AT1R) antagonist has proven to be effective reducing hypertension and renal damage; however, the mechanism by which AT1R blockade reduced kidney injury and normalizes blood pressure in this experimental model is still complete unknown. The current study was designed to test the hypothesis that AT1R activation promotes renal NAD(P)H oxidase up-regulation, oxidative stress and cytokine production during L-NAME induced-hypertension. Main methods Male Sprague–Dawley rats were distributed in three groups: L-NAME, receiving 70 mg/100 ml of L-NAME, L-NAME + Los, receiving 70 mg/100 ml of L-NAME and 40 mg/kg/day of Losartan; and Controls, receiving water instead of L-NAME or L-NAME and Losartan. Key findings After two weeks, L-NAME induced high blood pressure, renal overexpression of AT1R, NAD(P)H oxidase sub-units gp91, p22 and p47, increased levels of oxidative stress, interleukin-6 (IL-6) and interleukin-17 (IL-17). Also, we found increased renal accumulation of lymphocytes and macrophages. Losartan treatment abolished the renal expression of gp91, p22, p47, oxidative stress and reduced NF-κB activation and IL-6 expression. Significance These findings indicate that NO induced-hypertension is associated with up-regulation of NADPH oxidase, oxidative stress production and overexpression of key inflammatory mediators. These events are associated with up-regulation of AT1R, as evidenced by their reversal with AT1R blocker treatment.

In the present study, we have evaluated whether melatonin (MEL) modulates Mn-induced decrease in spontaneous motor activity (SMA) and lipid peroxidation, estimated as malondialdehyde (MDA) formation, in several brain regions. In mice treated with manganese a decrease in SMA after 2 weeks of treatment was observed. In the group treated with Mn+MEL a significant greater reduction in SMA was detected at 4 weeks. MDA levels were reduced in both MEL and Mn treated mice. In the animals treated with MEL + Mn a higher reduction in MDA levels was observed. These results suggest that MEL modulates the effect of Mn on SMA and brain lipid peroxidation.

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