title: Melatonin reduces renal interstitial inflammation and improves hypertension in spontaneously hypertensive rats.
abstract: 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.
authors.affiliation: Renal Service and Laboratory, Hospital Universitario, Instituto de Investigaciones Biomédicas (Fundacite-Zulia), Universidad del Zulia, Maracaibo 4001-A, Venezuela.
authors.forename: Mayerly
authors.initials: M
authors.lastname: Nava
authors.forename: Yasmir
authors.initials: Y
authors.lastname: Quiroz
authors.forename: Nosratola
authors.initials: N
authors.lastname: Vaziri
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rodriguez-Iturbe
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004326:Drinking / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D008214:Lymphocytes / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013481:Superoxides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D013481:Superoxides; D008550:Melatonin