Obesity induces hemodynamic and humoral changes that could be involved in the development of heart failure (HF) with preserved ejection fraction (HFpEF). Moreover, oxidative stress (OS) associated to obesity creates a vicious circle which amplifies cardiac disruptions.

Our study aimed at assessing cardiac function and oxidative stress markers in a rat model of heart failure and obesity.

Sprague-Dawley male rats (wild type, WT) and transgenic rats overexpressing β3-adrenergic receptors in endothelial cells (TGβ3) were either fed with standard diet (WT+SD, n=10; TGβ3+SD, n=10) or with hypercaloric diet (WT+HD, n=10; TGβ3+HD, n=10). For 35 weeks (W) echocardiography parameters were monitored. At the end of the study, the B-type natriuretic peptide (BNP) and oxidative stress markers (plasma hydroperoxides (“FORT” colorimetric test), nitrite and nitrate (NOx, spectrophotometrically) levels and cardiac expression of endothelial NO synthase (eNOS, Western blot)) were assessed.

The HD induced an increase in body weight in both HD-groups starting with W4 (+12%). Starting with W12, a decrease (P<0.05) in early-to-late LV diastolic relaxation ratio (eʹ/aʹ) in TGβ3+HD group (TGβ3+HD vs. WT+SD: 1.47±0.09 vs. 1.74±0.08) was observed, while for TGβ3+SD group this decline occurred later, in W25 (TGβ3+SD vs. WT+SD: 1.05±0.07 vs. 1.34±0.104). In W35, no significant change was registered in the ejection fraction (%) between all groups (∼64%), but a significant increase in plasma BNP was noted in both transgenic groups (Tgβ3+SD/Tgβ3+HD vs. WT+SD: 17.98±2.06/18.66±1.98 vs. 10.16±0.67pg/mL). Also, a significant increase in plasma hydroperoxide level was recorded in both groups of rats fed with HD, respectively a decrease in plasma NOx levels and cardiac eNOS expression (ratio eNOS/stain free: WT+SD=1±0.07, WT+HD=0.47±0.07, Tgβ3+HD=0.35±0.08, P<0.05).

The HD induces an earlier alteration (W12) in the diastolic function in obese TGβ3 rats as compared to normal-weight TGβ3 (W25) or with obese WT rats (W35). Also, the long-term intake of HD increased plasma lipid peroxidation and reduced the NO bioavailability with the decrease in cardiac expression of eNOS.