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Role of the NADPH oxidase in the regulation of cardiac NO bioactivity in response to a low salt diet
Author(s) -
Skayian Yester Sebouh,
Coffin Samuel,
Huang Harer,
Kaley Gabor,
Hintze Thomas H
Publication year - 2007
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.21.5.a524-b
Subject(s) - carbachol , apocynin , chemistry , nadph oxidase , stimulation , endocrinology , medicine , bradykinin , oxidase test , in vivo , enzyme , biochemistry , biology , receptor , microbiology and biotechnology
The objective of this study was to determine the effects of low salt diet on MVO 2 , ANG II and NO bioactivity in mice with defects in the expression of gp91 phox [gp91 phox (−/−)]. On normal diet, stimulation of NO production by bradykinin (BK, −21 ± 2%) or carbachol (−22 ± 1%) induced a concentration dependent reduction in MVO 2 in vitro in WT mice (n=5). BK‐ or carbachol‐induced reduction was significantly greater in gp91 phox (−/−) mice (−27 ± 1% at 10 −4 mol/l BK and −28 ± 2% at 10 −4 mol/l carbachol (n=5), P<0.05). The reduction in MVO 2 was significantly attenuated by L‐NAME in both WT and gp91 phox (−/−) mice, (P<0.05). Low salt diet increased plasma ANG II levels in WT mice (264 ± 27 to 476 ± 68 pg/ml (n=5), P<0.01) as well as in gp91 phox (−/−) mice (251 ± 32 to 395 ± 49 pg/ml (n=5), P<0.05). BK‐ or carbachol‐induced reduction in MVO 2 was significantly attenuated in WT mice (−7 ± 1% and −14 ± 1%, respectively) on low salt diet. No significant attenuation was seen in gp91 phox (−/−) mice on low salt diet; ie BK still reduced MVO 2 by −27 ± 3%. The attenuated BK‐ or carbachol‐induced reduction in MVO 2 was restored by apocynin in WT mice (−25 ± 1% and −27 ± 3%) on low salt diet but had no effect in gp91 phox (−/−) mice. Thus, low salt diet increases plasma ANG II, reduces NO bioavailability in the heart through activation and assembly of NADPH oxidase. Activation of the oxidase by ANG II may be the basis of low salt diet induced cardiovascular dysfunction. (Supported by PO‐1‐43023, HL 63129 and 83625).