title: iNOS inhibition improves autonomic dysfunction and oxidative status in hypertensive obese rats.
abstract: It has been suggested that nitric oxide (NO) from iNOS source is involved in inflammation and oxidative stress, and hypertension in obese subjects involves an inflammatory process. However, no study evaluated the participation of iNOS inhibition on cardiovascular, autonomic, and inflammatory parameters in obese rats. Obesity was induced by the administration of 4 mg/g body weight of monosodium glutamate (MSG) or equimolar saline (CTR) in newborn rats. On the 60th day, treatment with aminoguanidine (Amino, 50 mg/kg), an iNOS inhibitor, or 0.9% saline, was started. On the 90th day, mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious rats and autonomic modulation was conducted with the CardioSeries software. Plasma samples were collected to assess lipid peroxidation and prostaglandins (PGE2). In addition, iNOS immunohistochemistry in cardiac tissue was evaluated. MSG rats showed hypertension compared to CTR, and Amino treatment did not reverse it. Obese rats presented increased sympathetic and decreased parasympathetic modulation to the heart, reverted by Amino treatment. Plasma PGE2was increased in obese rats, and Amino treatment decreased. Obese rats presented increased plasma lipoperoxidation, which was decreased after Amino treatment. Also, cardiac iNOS immunohistochemistry was decreased after Amino treatment. Our data suggest that iNOS activation is involved in the systemic and cardiac mechanisms of oxidative stress, inflammation, and autonomic dysfunction derived from obesity.
authors.affiliation: a Department of Physiological Sciences , State University of Londrina , Londrina , Brazil.
authors.forename: Natalia Veronez
authors.initials: NV
authors.lastname: da Cunha
authors.affiliation: a Department of Physiological Sciences , State University of Londrina , Londrina , Brazil.
authors.forename: Fernanda Novi Cortegoso
authors.initials: FN
authors.lastname: Lopes
authors.affiliation: b Department of Pathological Sciences , State University of Londrina , Londrina , Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Panis
authors.affiliation: b Department of Pathological Sciences , State University of Londrina , Londrina , Brazil.
authors.forename: Rubens
authors.initials: R
authors.lastname: Cecchini
authors.affiliation: b Department of Pathological Sciences , State University of Londrina , Londrina , Brazil.
authors.forename: Phileno
authors.initials: P
authors.lastname: Pinge-Filho
authors.affiliation: a Department of Physiological Sciences , State University of Londrina , Londrina , Brazil.
authors.forename: Marli Cardoso
authors.initials: MC
authors.lastname: Martins-Pinge
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001341:Autonomic Nervous System / Q000187:drug effects; D015232:Dinoprostone / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D007249:Inflammation / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000737:chemistry; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000037:antagonists & inhibitors*; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012970:Sodium Glutamate
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D015232:Dinoprostone; C004479:pimagedine; D012970:Sodium Glutamate
keywords: Hypertension; inflammation; monosodium glutamate; nitric oxide; prostaglandins; sympathetic