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.

Evaluation of clinical variables associated with increased carotid intima-media thickness in middle-aged hypertensive women.

It has been previously documented that carotid intima-media thickness (cIMT) is a predictor of cardiovascular disease. The aim of this study was to identify clinical parameters associated with an increased cIMT treated hypertensive women. Female patients (n = 116) with essential hypertension, aged 40-65 years, were included in this study. Vascular ultrasound was performed and the patients were divided into two groups according to the values of cIMT (< or ≥0.9 mm). Patients with greater cIMT presented significantly higher systolic blood pressure and pulse pressure. Serum HDL-cholesterol was significantly lower and CRP was significantly higher in the same group. There was a significant correlation between cIMT and age (r = 0.25, P = 0.007), systolic blood pressure (r = 0.19, P = 0.009), pulse pressure (r = 0.30, P = 0.001), and LDL-cholesterol (r = 0.19, P = 0.043). cIMT was correlated to CRP (r = 0.31, P = 0.007) and negatively correlated to HDL-cholesterol (r = 0.33, P = 0.001). In logistic regression, only HDL-cholesterol, CRP, and pulse pressure were shown to be independent variables associated to increased cIMT. In conclusion, pulse pressure, HDL-cholesterol, and CRP are variables correlated with cIMT in treated hypertensive women.

Eplerenone offsets cardiac and aortic adverse remodeling in spontaneously hypertensive rats.

BACKGROUND: Several studies have shown beneficial effects of eplerenone in hypertension and left ventricular dysfunction, but its action on cardiac and vascular changes secondary to blood pressure elevation are not clear yet. METHODS: Twenty-five male spontaneously hypertensive rats (SHR) were assigned into five groups: young SHR (16 weeks), control SHR (22 weeks), and SHR treated by eplerenone (50 mg/kg/day), enalapril (10 mg/kg/day) or eplerenone+enalapril during 6 weeks. Five Wistar male rats were used as reference group. Cardiac structure and aorta were analyzed by stereology and image analysis. RESULTS: The raise of blood pressure (202+/-3 mm Hg in control SHR) was significantly attenuated by eplerenone (169+/-2 mm Hg) or enalapril (170+/-2 mm Hg, P<0.001 versus control SHR), and more intensely by combined therapy (160+/-2 mm Hg, P<0.01 versus eplerenone or enalapril). The number of cardiomyocytes in left ventricle was preserved in enalapril group (35,660+/-910 versus 16,220+/-730x10(3) in control SHR, P<0.01) but more significantly in eplerenone, alone or combined, groups (38,380+/-439 and 38,660+/-374x10(3), respectively, P<0.001 versus control). The increased connective tissue volume density (35.8+/-1.2%) noted in the left ventricle of control SHR was significantly attenuated by eplerenone (7.4+/-0.8%), enalapril (8.0+/-0.6%) or eplerenone+enalapril (6.0+/-1.1%, P<0.01 treated versus control SHR). Media-to-lumen ratio of intramyocardial arteries was reduced by enalapril, but more significantly by eplerenone alone or combined with enalapril. The increase of media cross-sectional area of aorta in control SHR was attenuated by eplerenone and/or enalapril. CONCLUSIONS: Eplerenone is effective in attenuating cardiovascular remodeling in SHR, confirming the important role of aldosterone in this process.