Melatonin reduces renal interstitial inflammation and improves hypertension in spontaneously hypertensive rats

Several studies have demonstrated that treatment with antioxidants improves hypertension in spontaneously hypertensive rats (SHR). Because our laboratory has shown that renal infiltration of immune cells plays a role in the development of hypertension (Rodriguez-Iturbe B, Quiroz Y, Nava M, Bonet L, Chavez M, Herrera-Acosta J, Johnson RJ, and Pons HA. Am J Physiol Renal Physiol 282: F191-F201, 2002), we did the present studies to define whether the antihypertensive effect of antioxidants was associated with an improvement in renal inflammation. Melatonin was administered as an antioxidant. For 6 wk, melatonin was added to the drinking water (10 mg/100 ml) given to a group of SHR (SHR-Mel; n = 10), and we compared them with groups of untreated SHR (n = 10) and Wistar-Kyoto (WKY) control rats (n = 10). Hypertension became increasingly severe in the SHR group [195 +/- 14.3 (SD) mmHg at the end of the experiment] and improved in the SHR-Mel group (149 +/- 20.4 mmHg, P < 0.001) in association with a 40-60% reduction in the renal infiltration of lymphocytes, macrophages, and angiotensin II-positive cells. Intracellular superoxide and renal malondialdehyde content were reduced by melatonin treatment as was the immunohistological expression of the 65-kDA DNA-binding subunit of NF-kappaB. We conclude that melatonin treatment ameliorates hypertension in SHR in association with a reduction in interstitial renal inflammation. Decreased activation of NF-kappaB, likely resulting from a reduction in local oxidative stress, may play a role in the suppression of renal immune infiltration and, thereby, in the antihypertensive effects of melatonin.