Anti-inflamatory effect of the S-nitroso-N-acetyleysteine (SNAC) on left ventricular hypertrophy in hypercholesterolemic LDLr/mice / Efeito antiinflamatorio da S-nitroso-N-acetilcisteina (SNAC) na hipertrofia ventricular esquerda (HVE) em camundongos hipercolesterolemicos knockout para o receptor de LDL (LDLr-/-)

AUTOR(ES)
DATA DE PUBLICAÇÃO

2006

RESUMO

Recently, it has been that S-nitroso-N-acetylcysteine (SNAC) attenuate in 55% the plaque development in low-density lipoprotein-receptor-deficient (LDLr-/-) mice fed a hypercholesterolemic diet for 15 days. The present study was designed to verify whether deletion of the low-density lipoprotein (LDL) receptor gene may affect the hemodynamic profile and adrenergic inotropic cardiac responses and, particularly, to identify the ability of SNAC to prevent the myocardial alterations and hypertension in hypercholesterolemic mice. C57BL6 wild-type (WT) and LDLr-/- male mice (S) were fed a commercial diet for 15 days. Control mice (S) showed 11 % blood pressure increase, 62% left atrial contractility decrease, CD40L overexpression and eNOS underexpression in comparison to WT. LDLr-/- mice which were fed for 15 days with 1,25% cholesterol, 20% of fat and 0.5% of colic acid enriched diet (Chol), showed significant left ventricular hypertrophy (LVH) versus S, which was characterized by: a) 1.25-fold increase in the LV weight (mg)/body weight (g) ratio (4.17±0.09 vs. 3.34±0.07 mg/g, respectively; p<0.05); b) increased cardiomyocyte diameter (25±0.6 vs. 19±0.7 Um, p<0.05); c) enhanced expression of the constitutive and inducible NOS isoforms and CD40L;d) increased collagen deposit; e) no alteration in the atrial contractile performance or responsiveness to norepinephrine. Administration of SNAC to Chol mice ( Chol +SNAC) (0.51 Umol/kg/day, for 15day, i.p.) prevented increases in the left ventricular weight/body weight ratio (3.38±0.23 mg/g), cardiomyocyte diameter (20±0.7 Um), collagen deposit, NOS isoforms and CD40L overexpression, but had no effect on increased blood pressure or atrial basal hypocontractility, although it recovered responsiveness to norepinephrine. In conclusion, the present study demonstrated that the deletion of the LDL receptor gene in mice determined hypertension and a marked left atrial contractile deficit. These findings may be related to oxidative stress, resulting from inflammation and eNOS underexpression. High-cholesterol diet promoted LVH in LDLr-/- mice associated with enhanced inflammatory and oxidant processes. SNAC prevented LVH by processes that involved decreased CD40L expression and NOS overexpression effects attenuating the ventricular structural alterations induced by hypercholesterolemia independent of hypertension. Histological quantization demanded the development of interactive software for image analysis of tissue samples. The software was designed to allow a user-oriented change of a chosen red, green and blue (RGB) staining in a standardized color that can be used to segment the image and calculate the fractional area of interest. Thus the method allows efficient, reliable and reproducible processing of tissue sections that is less time-consuming than conventional methods and can be performed with standard microscope and computer.

ASSUNTO(S)

camundongos knockout left ventricular hypertrophy s-nitrosotiol hipertrofia ventricular esquerda deficiencia em ldlr knockout ldlr deficient s-nitrosothiol mice

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