Open AccessS-Nitroso-N-Acetylcysteine (SNAC) Prevents Myocardial Alterations in Hypercholesterolemic LDL Receptor Knockout Mice by Antiinflammatory Action
Author(s) -
José Antônio Dias Garcia,
Leandro dos Santos,
André Luiz de Moura,
Kelly Fabiane Santos Ricardo,
Amarylis Wanschel,
Sı́lvia Mika Shishido,
Regina Célia Spadari-Bratfisch,
Heraldo Possolo de Souza,
Marta Helena Krieger
Publication year - 2008
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/fjc.0b013e31815c39d4
Subject(s) - contractility , medicine , endocrinology , enos , knockout mouse , ldl receptor , blood pressure , receptor , chemistry , cholesterol , nitric oxide , lipoprotein , nitric oxide synthase
We investigated the ability of S-nitroso-N-acetylcyseine (SNAC) to prevent structural and functional myocardial alterations in hypercholesterolemic mice. C57BL6 wild-type (WT) and LDL-R-/- male mice (S) were fed a standard diet for 15 days. LDL-R-/- mice (S) showed an 11% increase in blood pressure, 62% decrease in left atrial contractility, and lower CD40L and eNOS expression relative to WT. LDL-R-/- mice fed an atherogenic diet for 15 days (Chol) showed significant increased left ventricular mass compared to S, which was characterized by: (1) 1.25-fold increase in the LV weight/body weight ratio and cardiomyocyte diameter; (2) enhanced expression of the NOS isoforms, CD40L, and collagen amount; and (3) no alteration in the atrial contractile performance. Administration of SNAC to Chol mice (Chol + SNAC) (0.51 micromol/kg/day for 15 day, IP) prevented increased left ventricular mass, collagen deposit, NOS isoforms, and CD40L overexpression, but it had no effect on the increased blood pressure or atrial basal hypocontractility. Deletion of the LDL receptor gene in mice resulted in hypertension and a marked left atrial contractile deficit, which may be related to eNOS underexpression. Our data show that SNAC treatment has an antiinflammatory action that might contribute to prevention of structural and functional myocardial alterations in atherosclerotic mice independently of changes in blood pressure.