iNOS contributes to heart failure with preserved ejection fraction through mitochondrial dysfunction and Akt S-nitrosylation

•Combination of HDF and L-NAME induced cardiac mitochondrial dysfunction and HFpEF phenotype.•Both long-term and short-term iNOS inhibition mitigated mitochondrial dysfunction and oxidative stress in HFpEF heart.•Akt S-nitrosylation was involved into the development of HFpEF.•Both long-term and short-term iNOS inhibition reduced Akt S-nitrosylation and rescued HFpEF phenotype.