The Role Of Ang Ii - Nad(P)H Oxidase And Cardiac No Bioavailability In Response To A Low Salt Diet

The effects of low salt (LS) diet on ANG II, MVO2 and NO bioactivity were studied in mice with defects in the expression of p47phox (−/−) or gp91phox (−/−), the cytosolic and membrane‐bound subunits of NAD(P)H oxidase, respectively. LS diet increased plasma ANG II levels in WT (238±26 to 462±49 pg/ml) as well as in p47phox (−/−) (235±60 to 382±58 pg/ml) and in gp91phox (−/−) mice (251±32 to 395±49 pg/ml, all P<0.05). On normal diet (ND), stimulation of NO production by bradykinin (BK) or carbachol (CCH) induced a concentration dependent reduction in MVO2 (−24±2%) in vitro in WT mice. BK‐ or CCH induced reduction was significantly greater in p47phox (−/−) mice (−31±5%). The reduction in MVO2 was significantly (P<0.005) attenuated by L‐NAME in WT and p47phox (−/−) mice. Similar effects were seen in gp91phox (−/−) mice on ND. BK‐or CCH induced reduction in MVO2 was significantly attenuated in WT mice (−10±1% and −13±1% respectively, P<0.0001) on LS diet. No significant attenuation was seen in p47phox (−/−) as well as in gp91phox (−/−) mice on LS diet. The attenuated BK induced reduction in MVO2 was restored by apocynin in WT mice (−27±2%) or by losartan (−22±1%) on LS diet. These findings suggest that increased plasma ANG II levels with low salt diet reduce NO bioavailability through the assembly and activation of NAD(P)H oxidase by ANG II and this may be the basis of low salt diet induced cardiovascular dysfunction.