Efeito da metformina no remodelamento miocárdico e renal em ratos obesos com resistência à insulina

Abstract

Many evidences show that obesity is associated to structural and functional changes in the heart of human and animal models. Recent studies also show that human obesity is associated with vascular structural and functional modifications, specially at large and medium-sized arteries. Epidemiological studies have confirmed that obesity is a significant risk factor for the development of proteinuria and end-stage renal disease in a normal population. With the objective to determinate morphological changes related to cardiac, vascular and renal remodeling in an experimental model of monosodium glutamate (MSG)-induced obesity and the effect of metformin at this finding. Twenty five rats were studied and divided into five groups: control with 16 e 22 weeks (CON-16 and CON-22); obese with 16 and 22 weeks (MSG-16 e MSG-22), and obese + metformin (MET-22) 300mg/Kg/day per oral. The characterization of insulin resistance was done through measurement of plasma insulin and calculation of HOMA-IR index. The morphological analysis and the quantification of myocardial collagen were carried out by Image Pro Plus analysis system. The systolic blood pressure was slightly higher in MSG-22 group, reaching statistical significance when compared to MSG-16 group (122±2 vs 108±2 mmHg, p<0.05). On the other hand, the MET-22 group demonstrated lower blood pressure levels (118±1 mmHg), without reaching statistical difference. The obese animals presented increase in media-to-lumen ratio with 16 weeks (39.9±3.7 vs 30.2±2.0 %, p<0.05) and with 22 weeks (39.8±1.3 vs 29.5±1.2%, p<0.05), which was reduced with use of metformin (31.5±0.9%). The collagen deposition in perivascular area of left ventricle was significantly greater in MSG-22 group (1.39±0.06 vs 0.83±0.06 % in CON-22, p<0.01), and attenuated by metformin (1.02±0.04%). In the kidney, the media cross-sectional area of intrarenal arterioles was similar among the groups (18.5±2.2 in CON-16; 19.9±3.7 in MSG-16; 18.9±3.1 in CON-22; 21.8±1.5 in MSG-22; 20.2±1.4 in MET-22). An increase of glomerular area was observed in MSG-22 group (141.3±4.5 vs 129.5±0.5 µm2), but without statistical significance. In conclusion, rats with MSG-induced obesity and insulin resistance presented more pronounced cardiac changes than renal alterations. In the heart, there were evidences of hypertrophic vascular remodeling were observed in intramyocardial small arteries and perivascular fibrosis. These findings were, at least partially, attenuated by metformin for six weeks, suggesting that this drug may be beneficial for prevention of cardiac, vascular and renal complications associated with obesity.