Role Of The Nadph Oxidase In The Regulation Of Cardiac No Bioactivity In Response To A Low Salt Diet

The objective of this study was to determine the effects of low salt diet on MVO2, ANG II and NO bioactivity in mice with defects in the expression of gp91phox [gp91phox (−/−)]. On normal diet, stimulation of NO production by bradykinin (BK, −21 ± 2%) or carbachol (−22 ± 1%) induced a concentration dependent reduction in MVO2 in vitro in WT mice (n=5). BK- or carbachol-induced reduction was significantly greater in gp91phox (−/−) mice (−27 ± 1% at 10−4mol/l BK and −28 ± 2% at 10−4mol/l carbachol (n=5), P<0.05). The reduction in MVO2 was significantly attenuated by L-NAME in both WT and gp91phox (−/−) 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 gp91phox (−/−) mice (251 ± 32 to 395 ± 49 pg/ml (n=5), P<0.05). BK- or carbachol-induced reduction in MVO2 was significantly attenuated in WT mice (−7 ± 1% and −14 ± 1%, respectively) on low salt diet. No significant attenuation was seen in gp91phox (−/−) mice on low salt diet; ie BK still reduced MVO2 by −27 ± 3%. The attenuated BK- or carbachol-induced reduction in MVO2 was restored by apocynin in WT mice (−25 ± 1% and −27 ± 3%) on low salt diet but had no effect in gp91phox (−/−) 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).