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 O(2)(*-) could enhance the NO(*)/O(2)(*-) 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(*)/O(2)(*-) 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 O(2)(*-) 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 O(2)(*-) 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(*)/O(2)(*-) balance by lowering vascular O(2)(*-) 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(*)/O(2)(*-) balance in males to a state similar to that in females.