Background: Overexpression of inducible nitric oxide synthase (iNOS) is a key link between
high-fat (HF) diet induced obesity and cardiovascular disease. Oestradiol has cardioprotective effects
that may be mediated through reduction of iNOS activity/expression.
Methods: In the present study, female Wistar rats were fed a standard diet or a HF diet (42% fat) for 10
weeks. iNOS gene and protein expressions were measured in heart tissue. HF-fed rats exhibited a
significant increase in cardiac iNOS mRNA by 695% (p<0.05), iNOS protein level by 248% (p<0.01),
without changes in nitrate/nitrite levels. Expression of CD36 protein in plasma membranes was
increased by 37% (p<0.05), while the concentration of free fatty acids (FFA) was reduced by 25%
(p<0.01) in HF-fed rats. Expression of the p50 subunit of nuclear factor-κB (NFκB-p50) in heart was
increased by 77% (p<0.01) in HF-fed rats. Expression of protein kinase B (Akt) and extracellular signalregulated
kinases 1/2 (ERK1/2) were unchanged between the groups. There was a significant increase in
the ratio of phospho-Akt/total Akt but not for phospho-ERK1/2/total ERK1/2 in HF-fed rats. Estrogen
receptor-α levels (by 50%; p<0.05) and serum oestradiol concentrations (by 35%; p<0.05) were shown
to be significantly reduced in HF-fed rats.
Results and Conclusion: Our results revealed that a HF diet led to increased iNOS expression, most
likely via a mechanism involving Akt and NFκB-p50 proteins. Decreased levels of oestradiol and ERα
protein in the HF-fed group, in combination with increased iNOS levels are consistent with the
hypothesis that oestradiol has a cardioprotective effect through its ability to regulate iNOS expression.