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The aims of this study were to investigate the effects of melatonin and N-acetylcysteine on the baroreflex sensitivity and to verify whether those effects were correlated with their antioxidant capacity in Wistar-Kyoto and spontaneously hypertensive rats (SHR).Rats were treated with 30 mg/kg/day of melatonin or 4 g/kg/day of N-acetylcysteine for 4 weeks. Changes in mean arterial pressure, heart rate, plasma norepinephrine, and epinephrine were measured in conscious rats after an intravenous injection of phenylephrine or sodium nitroprusside.The SHR were characterized by decreased reflex chronotropic responses to phenylephrine and sodium nitroprusside (P < .001 and P < .001), as well as by an enhanced increase in plasma catecholamine concentrations in response to sodium nitroprusside (P < .001). Melatonin and N-acetylcysteine produced a significant reduction in mean arterial pressure and heart rate in SHR (P < .001). Melatonin and N-acetylcysteine improved bradycardic (P < .001) and tachycardic (P < .001) baroreflex responses in SHR without modifying catecholamine responses. The antioxidant reserve, which was reduced in SHR as reflected by the lower glutathione peroxidase activity in plasma (P < .05), was normalized by N-acetylcysteine and melatonin (P < .05). N-acetylcysteine (P < .001) and melatonin (P < .05) increased glutathione peroxidase activity in erythrocytes from SHR.The results of the present study suggest that melatonin and n-acetylcysteine improve the baroreflex response in SHR in correlation with the antioxidant effects of these substances.