title: Simvastatin reverses target organ damage and oxidative stress in Angiotensin II hypertension: comparison with apocynin, tempol, and hydralazine.
abstract: The ability of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor simvastatin to reverse established cardiovascular and renal alterations and oxidative stress was assessed in angiotensin II (AngII) hypertension. Sprague-Dawley rats infused with AngII (200 ng/kg per minute for 17 days) were concomitantly treated or not for the last 7 days with simvastatin, apocynin, tempol, and hydralazine (60, 60, 30, and 15 mg/kg per day, respectively). Only hydralazine lowered AngII hypertension. Simvastatin and apocynin lowered cardiac hypertrophy by 52% and 54% and reversed the marked rise in albuminuria by 25% and 70%. Neither tempol nor hydralazine affected cardiac mass or albuminuria. None of the treatments modified the AngII-induced increase in carotid media thickness. The rise in cardiac superoxide anion production (lucigenin-enhanced chemiluminescence method) induced by AngII was reversed by all treatments. Enhanced plasma concentration of advanced oxidation protein products (spectrophotometry using chloramine T) was unaffected by simvastatin and tempol, but it was reversed by apocynin and hydralazine. Our results indicate that simvastatin reverse established cardiac and renal alterations in AngII hypertension independently of arterial pressure. It is suggested that oxidative stress participates in the maintenance of target organ damage and that antioxidant properties are involved in the beneficial influence of the statin.
authors: Groupe Rein Hypertension, Laboratoire de Nutrition Humaine et Athérogénèse Institut Universitaire de Recherche Clinique, Université de Montpellier I, France.
authors: Caroline
authors: C
authors: Rugale
authors: Sandrine
authors: S
authors: Delbosc
authors: Albert
authors: A
authors: Mimran
authors: Bernard
authors: B
authors: Jover
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000419:Albuminuria / Q000139:chemically induced / Q000188:drug therapy; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology*; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D017540:Tunica Media / Q000187:drug effects / Q000503:physiopathology
chemical_list: D000098:Acetophenones; D000959:Antihypertensive Agents; D000975:Antioxidants; D003497:Cyclic N-Oxides; D000960:Hypolipidemic Agents; D013113:Spin Labels; D013481:Superoxides; D000804:Angiotensin II; D006830:Hydralazine; D019821:Simvastatin; C056165:acetovanillone; C001803:tempol