Regional Expression of NAD(P)H Oxidase and Superoxide Dismutase in the Brain of Rats with Neurogenic Hypertension

Abstract

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 (O₂^–·¿ ) in noradrenergic control of arterial pressure. Since NAD(P)H oxidase is a major source of O₂^–·¿ , 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 O₂^–·¿ 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.