Exercise training reduces cardiac dysfunction and remodeling in ovariectomized rats submitted to myocardial infarction.

The aim of this study was to evaluate whether exercise training (ET) prevents or minimizes cardiac dysfunction and pathological ventricular remodeling in ovariectomized rats subjected to myocardial infarction (MI) and to examine the possible mechanisms involved in this process. Ovariectomized Wistar rats were subjected to either MI or fictitious surgery (Sham) and randomly divided into the following groups: Control, OVX+SHAMSED, OVX+SHAMET, OVX+MISED and OVX+MIET. ET was performed on a motorized treadmill (5x/wk, 60 min/day, 8 weeks). Cardiac function was assessed by ventricular catheterization and Dihydroethidium fluorescence (DHE) was evaluated to analyze cardiac oxidative stress. Histological analyses were made to assess collagen deposition, myocyte hypertrophy and infarct size. Western Blotting was performed to analyze the protein expression of catalase and SOD-2, as well as Gp91phox and AT1 receptor (AT1R). MI-trained rats had significantly increased in +dP/dt and decreased left ventricular end-diastolic pressure compared with MI-sedentary rats. Moreover, oxidative stress and collagen deposition was reduced, as was myocyte hypertrophy. These effects occurred in parallel with a reduction in both AT1R and Gp91phox expression and an increase in catalase expression. SOD-2 expression was not altered. These results indicate that ET improves the functional cardiac parameters associated with attenuation of cardiac remodeling in ovariectomized rats subjected to MI. The mechanism seems to be related to a reduction in the expression of both the AT1 receptor and Gp91phox as well as an increase in the antioxidant enzyme catalase, which contributes to a reduction in oxidative stress. Therefore, ET may be an important therapeutic target for the prevention of heart failure in postmenopausal women affected by MI.

Cardiac fibrosis and vascular remodeling are attenuated by metformin in obese rats.

BACKGROUND: Human obesity has been associated with alterations of vascular structure, especially in large and medium arteries, but the effects of insulin-sensitizers are not well known. METHODS: Twenty-five male Wistar rats received subcutaneous injections of monosodium glutamate (MSG) or an equivalent volume of vehicle from the second to the sixth day after birth, At 16 weeks of age, five MSG rats started receiving an oral treatment with metformin (300 mg/kg) which was maintained for six weeks, composing five groups: control 16 weeks (CON-16), MSG 16 weeks (MSG-16), control 22 weeks (CON-22), MSG 22 weeks (MSG-22), and MSG plus metformin 22 weeks (MET-22). Systolic blood pressure (BP) was verified weekly. The lumen diameter and media thickness, media cross-sectional area (CSA) and growth index of the intramyocardial arterioles were measured. Cardiac interstitial and perivascular collagen density were also evaluated. RESULTS: Systolic BP was significantly increased in the MSG-22 comparing to MSG-16 group. Insulin resistance was confirmed by HOMA-IR index and metformin-treated group presented reduction of insulin levels at week 22. The morphology analysis showed greater media-to-lumen ratio and CSA in the obese groups, which were reduced by the metformin treatment. Connective tissue deposition in the perivascular region of the left ventricle was significantly higher in the obese groups which was attenuated by metformin. CONCLUSIONS: Hypertrophic vascular remodeling and cardiac collagen deposition were significantly evident in MSG-induced obese rats. Metformin treatment was able to reduce insulin resistance and attenuated this adverse cardiac and vascular remodeling.

La sobreexpresión del gen de enzima convertidora de angiotensina homóloga (ECA2) revierte la hipertensión arterial y el remodelado cardíaco experimental / Over expression of the homologous angiotensin converting enzyme (ACE2) gene reverts experimental hypertensión and cardiac remodeling

Antecedentes: La sobreexpresion génica de la enzima convertidora de angiotensina I homologa (ECA2) se asocia con prevención de la hipertrofia y fibrosis cardiaca dependiente de angiotensina (Ang) II. Sin embargo se desconoce si su sobreexpresion reduce la hipertensión arterial (HTA) y revierte el consecuente remodelado miocárdico (RM) dependiente de Ang II. Objetivo: Determinar si la sobreexpresion adenoviral (Ad) del gen de la ECA2 en el miocardio disminuye la HTA y RM experimental en ratas con niveles genéticamente determinados de ECA y Ang II. Métodos: Ratas homocigotas normotensas Lewis (LL) y Brown Borway (BN), con menores y mayores niveles circulantes de ECA y Ang II, respectivamente, se hicieron hipertensas por el procedimiento Goldblatt (GB). Como controles se usaron ratas seudo-operadas (sham). A la semana 5 post cirugía y con HTA establecida > 140 mmHg, las ratas se randomizaron a inyección intramiocárdica con un AdECA2 o Ad proteína fluorescente verde (GFP) como controles de infección. A la semana post infección adenoviral, los ratas se sacrificaron y se determinaron peso corporal (PC, g), masa cardiaca (MC, mg), presión arterial sistólica (RAS, mmHg), área (AC, um2) y perímetro (PERC, um) de cardiomiocitos y contenido de colágeno ( por ciento) miocárdico (CM), sub-endocárdico (CS)ytotal(CT). Resultados: La HTA aumentó significativamente la MC, MCR, AC, PERC como también el CM, CS y CT en las ratas GB vs Sham, sin diferencias en el PC ni por efecto del polimorfismo de la ECA. La sobreexpresion de ECA2 disminuyó significativamente la RAS (15 por ciento y 27 por ciento), AC (25 por ciento y 25 por ciento ) y PERC (17 por ciento y 18 por ciento) en las ratas LL y BN vs ratas hipertensas, respectivamente. Estos resultados se asociaron a una disminución significativa del CS (LL = 37 por ciento, BN = 39 por ciento), CM (LL = 54 por ciento) y CT (LL = 42 por ciento, BN = 22 por ciento) respecto a las ratas GB. Conclusión: En ratas con HTA...

Objective Background. Over expression of the gene for homologous angiotensin I converting enzyme (ACE) is associated with prevention of angiotensin II dependent cardiac hypertrophy and fibrosis. Whether this over expression is able to reduce hypertension and revert cardiac remodeling is unknown. Aim: To determine whether adenoviral ACE2 gene over expression in the myocardium decreases experimental hypertension and cardiac remodeling in rats with genetically determined levels of ACE and ANGII. Methods: Homozygous normotensive Lewis (LL) and Brown Norway (BN) rats with decreased or increased levéis of ACE and Ang II, respectively, were made hy-pertensive using the Goldblatt procedure. Sham opera-ted rats were used as control s. 5 weeks after surgery, when systolic blood pressure reached > 140 mmHg, rats were randomized to receive intramyocardial injec-tion of either AdACE2 or green fluorescent Ad protein (GFP) as infection controlling agents. One week after adenoviral infection, rats were sacrificed. Body weight (BW, Gr), relative cardiac mass (RCM, mG), systolic blood pressure (SBP, mmHg), cardiomyocite área (MA um2) and perimeter (MPER, uM), and myocardial co-llagen content, both subendocardial (SC, percent) and total (TC percent) were measured. Results: Hypertension was associated to significant in-creases in total and RCM, MA, MPER as well as SC and TC in Goldblatt vs normal rats. This was independent of BW and not affected by ACE polymorphism. ACE II over expression significantly decreased SBP (27 vs 15 percent), MA (25 vs 25 percent) and MPER (18 vs 17 percent) hy-pertensive vs normal rats, respectively. Conclusion: Over expression of ACE2 decreased hypertension, hypertrophy and fibrosis in rats with experimental hypertension and different levels of ACE and Ang II. (Fondecyt 1070662).

Effect of captopril on the prevention and regression of myocardial cell hypertrophy and interstitial fibrosis in pressure overload cardiac hypertrophy.

This article reports on the effects of captopril on both the prevention and the regression of myocardial cell hypertrophy and interstitial fibrosis in experimental animals (rats) with pressure overloaded hearts. Constriction of the abdominal aorta just below the diaphragm during periods of 20 days (prevention experiment) and 40 days (regression experiment) resulted in hypertension and cardiac hypertrophy. In the prevention experiment, captopril was able to inhibit the development of high blood pressure levels and cardiac hypertrophy in aortic-constricted rats. Similarly, the treatment of sham-operated rats with captopril led to a reduction in the weight of the heart and in the myocyte diameter compared with controls. The myocyte volume fraction of the left ventricles of both aortic-constricted and sham-operated animals that were treated with captopril was significantly diminished compared with that of the control group. The interstitial collagen volume fraction of all experimental groups was elevated as compared with the control group. As a consequence, the ratios of myocytes to interstitial collagen in groups of aortic-constricted rats, aortic-constricted rats that were treated with captopril, and sham-operated rats that were treated with captopril were reduced compared with the control group; that is, although captopril was able to prevent myocardial cell hypertrophy after aortic constriction, it could not prevent the maintenance of a normal ratio of myocytes to interstitial collagen, which was due to increased collagen volume fraction. In the regression experiment, captopril lowered high blood pressure levels and augmented heart weights to control values. The mean myocyte transverse diameter in aortic-constricted rats that were treated with captopril was significantly smaller than that of controls.(ABSTRACT TRUNCATED AT 250 WORDS)