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.

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The present study evaluated the effect of magnesium sulfate (MgSO4) on forced swim-induced thermal hyperalgesia in male Sprague-Dawley rats. Two schemes of MgSO4 administration were used: a preemptive scheme (100 mg/kg i.p. before each forced swim) and a therapeutic scheme (a single dose of 100 mg/kg, 24 hours after the final forced swim); pharmacological controls received normal saline. Thermal nociception was determined using the hot plate test, and lumbar spinal levels of nitric oxide (NO) metabolites were measured. Thermal hyperalgesia was present in forced swim animals treated with saline before each forced swim, but absent in forced swim animals preemptively treated with MgSO4. We could not determine an anti-hyperalgesic effect of the therapeutic scheme since MgSO4 tended to produce analgesia when administered one hour before the hot plate test, probably due to an acute stress response caused by the injection. On the other hand, non-stressed animals preemptively treated with MgSO4 displayed significantly higher levels of NO metabolites than forced swim animals preemptively treated with MgSO4 or saline and non-stressed animals preemptively treated with saline. The results suggest that MgSO4 can prevent the development of persistent pain states, but is unable to revert already established ones, a potential feature in patients suffering from anxiety, depression and chronic stress exposure; likewise, they indicate that the effect of MgSO4 on nociception is independent of an induction of NO synthesis.

We present a new sequential contingent strategy for DS screening and demonstrate its usefulness for reducing FPR while maintaining a high level of Sen for DS, without requiring an increase in economic costs.