Short-term hypercaloric diet induces blunted aortic vasoconstriction and enhanced vasorelaxation via increased nitric oxide synthase 3 activity and expression in Dahl salt-sensitive rats.

aimTo elucidate the role of the O(2)(-), H(2)O(2) or NO pathways in aortic angiotensin (Ang)II-induced vasoconstriction in Dahl salt-sensitive (SS) rats compared with control SS-13(BN) rats on a normal or hypercaloric diet.

methodsAortic function was assessed using wire myography in 16-week-old rats maintained on a normal diet or a 4-week hypercaloric diet. Nitric oxide synthase (NOS) activity and expression was determined by the conversion of radio-labelled arginine to citrulline and Western blot analysis respectively.

resultsOn normal diet, AngII-induced vasoconstriction was greater in SS than SS-13(BN) rats. Polyethylene glycol superoxide dismutase (PEG-SOD) reduced the aortic AngII response similarly in both strains on normal diet. Catalase blunted, whereas N(ω)-Nitro-L-arginine methyl ester (L-NAME) did not affect the AngII response in SS rats. In SS-13(BN) rats, catalase had no effect and L-NAME enhanced AngII response. On hypercaloric diet, aortic AngII responsiveness was reduced in SS but unaltered in SS-13(BN) rats compared with their normal diet counterparts. PEG-SOD reduced the AngII response in both rats on hypercaloric diet. Catalase treatment did not alter aortic AngII response, while L-NAME increased the response in SS rats on hypercaloric diet. In SS-13(BN) rats on hypercaloric diet, catalase reduced and L-NAME did not alter the AngII response. Furthermore, aortic endothelial-dependent vasorelaxation was increased in SS rats on hypercaloric diet compared with normal diet and aortic NOS3 activity and expression was increased.

conclusionA short-term hypercaloric diet induces a blunted vasoconstrictive and enhanced vasodilatory phenotype in SS rats, but not in SS-13(BN) rats, via reduced H(2)O(2) and increased NOS3 function.