S-nitroso-N-acetylcysteine (SNAC) prevents myocardial alterations in hypercholesterolemic LDL receptor knockout mice by antiinflammatory action.
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.
Garcia
José Antonio D
JA
Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, Brasil.
dos Santos
Leandro
L
Moura
André L
AL
Ricardo
Kelly Fabiane S
KF
Wanschel
Amarylis Claudine B A
AC
Shishido
Silvia M
SM
Spadari-Bratfisch
Regina C
RC
de Souza
Heraldo P
HP
Krieger
Marta H
MH
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D023201:CD40 Ligand / Q000187:drug effects / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000517:prevention & control*; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009200:Myocardial Contraction / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics*
D000893:Anti-Inflammatory Agents; D011973:Receptors, LDL; D023201:CD40 Ligand; C024940:S-nitroso-N-acetylcysteine; D052250:Nitric Oxide Synthase Type III; D000111:Acetylcysteine