Male Wistar Rats Chronically Fed with a High-Fat Diet Develop Inflammatory and Ionic Transport Angiotensin-(3–4)-Sensitive Myocardial Lesions but Preserve Echocardiographic Parameters

The central aim of this study was to investigate whether male Wistar rats chronically fed a high-fat diet (HFD) over 106 days present high levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and Na⁺ and Ca²⁺ transport alterations in the left ventricle, together with dyslipidemia and decreased glucose tolerance, and to investigate the influence of Ang-(3-4). The rats became moderately overweight with an expansion of visceral adiposity. Na⁺-transporting ATPases, sarco-endoplasmic reticulum Ca²⁺-ATPase (SERCA2a), and the abundance of Angiotensin II receptors were studied together with lipid and glycemic profiles from plasma and left-ventricle echocardiographic parameters fractional shortening (FS) and ejection fraction (EF). IL-6 and TNF-α increased (62% and 53%, respectively), but returned to normal levels with Angiotensin-(3-4) administration after 106 days. Significant lipidogram alterations accompanied a decrease in glucose tolerance. Angiotensin II receptors abundance did not change. (Na⁺ + K⁺)ATPase and ouabain-resistant Na⁺-ATPase were downregulated and upregulated, respectively, but returned to normal values upon Angiotensin-(3-4) administration. SERCA2a lost its ability to respond to excess ATP. Echocardiography showed no changes in FS or EF. We conclude that being overweight causes an increase in Ang-(3-4)-sensitive IL-6 and TNF-α levels, and ion transport alterations in the left ventricle that could evolve into future heart dysfunction.