Premium
The role of ANG II ‐ NAD(P)H oxidase and cardiac NO bioavailability in response to a low salt diet
Author(s) -
SkayianErvolina Yester,
Huang Harer,
Hintze Thomas H
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.643.12
The effects of low salt (LS) diet on ANG II, MVO 2 and NO bioactivity were studied in mice with defects in the expression of p47 phox (−/−) or gp91 phox (−/−), 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 p47 phox (−/−) (235±60 to 382±58 pg/ml) and in gp91 phox (−/−) 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 MVO 2 (−24±2%) in vitro in WT mice. BK‐ or CCH induced reduction was significantly greater in p47 phox (−/−) mice (−31±5%). The reduction in MVO 2 was significantly (P<0.005) attenuated by L‐NAME in WT and p47 phox (−/−) mice. Similar effects were seen in gp91 phox (−/−) mice on ND. BK‐or CCH induced reduction in MVO 2 was significantly attenuated in WT mice (−10±1% and −13±1% respectively, P<0.0001) on LS diet. No significant attenuation was seen in p47 phox (−/−) as well as in gp91 phox (−/−) mice on LS diet. The attenuated BK induced reduction in MVO 2 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. Supported by HL 43023.