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

Abstract

Aim: To 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.

Methods: Aortic 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.

Results: On 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.

Conclusion: A 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.

Figure 1

Angiotensin (Ang)II-mediated vasoconstriction in aortas from SS-13^BN rats normal diet (N=12) or hyper-caloric diet (N=10) or SS rats on normal diet (N=8) or hyper-caloric diet (n=14). *P<0.05 for E_max in aortic segments from SS rats on normal diet vs. hyper-caloric diet; †P<0.05 for E_max in aortic segments SS rats vs. SS-13^BN rats on normal diet.

Figure 2

Angiotensin (Ang)II-mediated vasoconstriction in aortas from SS-13^BN rats (A: normal diet: untreated N=11, +PEG-SOD N=6; hyper-caloric diet: untreated N=10, +PEG-SOD N=3) (C: normal diet: untreated N=11, +CATALASE N=4; hyper-caloric diet: untreated N=10, +CATALASE N=4). AngII vasoconstriction in aortas from SS rats (B: normal diet: untreated N=8, +PEG-SOD N=6; hyper-caloric diet: untreated N=14, +PEG-SOD N=9). (D: normal diet: untreated N=8, +CATALASE N=5; hyper-caloric diet: untreated N=14, +CATALASE N=12). *P<0.05 for E_max in aortic segments in corresponding untreated groups.

Figure 3

A: Angiotensin (Ang)II-mediated vasoconstriction in aortas from SS-13^BN rats on normal diet (untreated N=12, +L-NAME N=6) or hyper-caloric diet (untreated N=10, +L-NAME N=5). B: AngII vasoconstriction in aortas from SS rats on normal diet (untreated N=8, +L-NAME N=6) or hyper-caloric diet (untreated N=14, +L-NAME N=11). *P<0.05 for E_max in L-NAME-treated vs. untreated aortic segments from SS-13^BN rats on normal diet. †P<0.05 for E_max in L-NAME-treated vs. untreated aortic segments from SS rats on hyper-caloric diet.

Figure 4

Acetylcholine (ACh)- and sodium nitroprusside (SNP)-mediated vasorelaxation in SS-13^BN rats (A and B, respectively; normal diet: untreated N=10, +L-NAME N=10; hyper-caloric diet: untreated N=9, +L-NAME N=9) and SS rats (C and D, respectively; normal diet: untreated N=8, +L-NAME N=8; hyper-caloric diet: untreated N=8–14, +L-NAME N=14). *P<0.05 E_max vs. SS rats on normal diet.

Figure 5

In aortic tissue from SS rats, A: AT1R expression (normal diet N=8; hyper-caloric diet N=8), B: NOS3 protein expression (normal diet N=7; hyper-caloric diet N=7), and C: NOS activity (normal diet N=3; hyper-caloric diet N=4). *P<0.05 vs. SS rats on normal diet.