Gender-specific effects of caloric restriction on the balance of vascular nitric oxide and superoxide radical

Aims Caloric restriction (CR) and female gender attenuate oxidative damage and improve vascular endothelium-dependent relaxation (EDR). Multiple mechanisms that ameliorate vascular O2^•- could enhance the NO ^•/O2^•- balance and thus improve EDR. The aim of this study is to compare the effects of short-term (2 weeks) CR and gender on molecular mechanisms involved in NO^•/O2^•- balance and EDR. Methods and results Wistar rats (8 weeks old) of both genders were fed ad libitum (control) or were subjected to CR (60 of food intake of controls) for 2 weeks. Plasma levels of NO^•, insulin, and ghrelin, EDR, vascular NO^• and O2^•- production, as well as endothelial NO^• synthase (eNOS) and NADPH oxidase (Nox) expression were examined and analysed. CR improved EDR and vascular NO^• levels and ameliorated NADPH-sensitive O2^•- production in male rats more than in females. Both CR and female gender reduced mRNA expression of Nox1 and Nox p22phox (p22phox); however, CR reduced Nox4 and p47phox only in males. Protein expression studies showed that CR enhanced eNOS and reduced Nox4 only in males. Conclusion Short-term CR improved the NO ^•/O2^•- balance by lowering vascular O2 ^•- production through decreased expression of Nox in males, thus enhancing bioactive NO^• levels and EDR. In this regard, CR shifted the state of vascular NO^•/O2^•- balance in males to a state similar to that in females.