The work detailed here demonstrated that the impact of summer in guinea‐pigs and rats, and of diabetes in rats, resulted in: (1) increased cardiac O2− production and reduced plasma nitrite concentration, denoting oxidative stress and endothelial dysfunction, respectively; (2) myocardial upregulation of the O2−forming Noxs and the downregulation of Nox4, and (3) myocardial induction of the NF‐κB pathway and repression of the Nrf2 pathway. The gene discussed is NOX4; the disease is endothelial dysfunction.