Regional expression of NAD(P)H oxidase and superoxide dismutase in the brain of rats with neurogenic hypertension.
BACKGROUND
Single injection of small quantities of phenol into the kidney cortex causes hypertension which is mediated by renal afferent sympathetic pathway activation. This phenomenon can be prevented by superoxide dismutase (SOD) infusion in the lateral ventricle, suggesting the role of superoxide (O(2)(-).) in noradrenergic control of arterial pressure. Since NAD(P)H oxidase is a major source of O(2)(-)., we tested the hypothesis that hypertension in this model may be associated with upregulation of NAD(P)H oxidase in relevant regions of brain.


METHODS
NAD(P)H oxidase subunits, mitochondrial (MnSOD) and cytoplasmic (CuZnSOD) SOD were measured in rats 4 weeks after injection of phenol or saline in the left kidney cortex.


RESULTS
Phenol-injected rats exhibited hypertension, upregulation of gp91(phox), p22(phox), p47(phox) and p67(phox) in the medulla, gp91(phox) and p22(phox) in pons and gp91(phox) in hypothalamus. This was associated with upregulation of MnSOD with little change in CuZnSOD.


CONCLUSIONS
Chronic hypertension in phenol-injected rats is associated with upregulation of NAD(P)H oxidase and hence increased O(2)(-). production capacity in the key regions of the brain involved in regulation of blood pressure. Since reactive oxygen species can intensify central noradrenergic activity, the observed maladaptive changes may contribute to the genesis and maintenance of the associated hypertension.
Bai
Yongli
Y
Division of Nephrology and Hypertension, University of California-Irvine, 101 The City Drive, Orange, CA 92868, USA.
Jabbari
Bahman
B
Ye
Shaohua
S
Campese
Vito M
VM
Vaziri
Nosratola D
ND
D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000201:enzymology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D019800:Phenol / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism*
D019800:Phenol; D013482:Superoxide Dismutase; D019255:NADPH Oxidases