Oxidative stress mediates the stimulation of sympathetic nerve activity in the phenol renal injury model of hypertension.
Renal injury caused by the injection of phenol in the lower pole of one kidney increases blood pressure (BP), norepinephrine secretion from the posterior hypothalamic nuclei (PH), and renal sympathetic nerve activity in the rat. Renal denervation prevents these effects of phenol. We have also demonstrated that noradrenergic traffic in the brain is modulated by NO and interleukin-1beta. In this study, we tested the hypothesis that the increase in sympathetic nervous system (SNS) activity in the phenol renal injury model is because of activation of reactive oxygen species. To this end, first we examined the abundance of several components of reduced nicotinamide-adenine dinucleotide phosphate oxidase (identified as the major source of reactive oxygen species), including gp91phox/Nox2, p22phox, p47phox, and Nox3 using real-time PCR. Second, we evaluated the effects of 2 superoxide dismutase mimetic, tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl), and superoxide dismutase-polyethylene glycol on central and peripheral SNS activation caused by intrarenal phenol injection. Intrarenal injection of phenol raised BP, NE secretion from the PH, renal sympathetic nerve activity, and the abundance of reduced nicotinamide-adenine dinucleotide phosphate and reduced the abundance of interleukin-1beta and neural-NO synthase mRNA in the PH, paraventricular nuclei, and locus coeruleus compared with control rats. When tempol or superoxide dismutase-polyethylene glycol were infused in the lateral ventricle before phenol, the effects of phenol on BP and SNS activity were abolished. The studies suggest that central activation of the SNS in the phenol-renal injury model is mediated by increased reactive oxygen species in brain nuclei involved in the noradrenergic control of BP.
Ye
Shaohua
S
Division of Nephrology, Hypertension Center, Keck School of Medicine, University of Southern California, 1200 North State St, Los Angeles, CA 90033, USA.
Zhong
Huiquin
H
Yanamadala
Swati
S
Campese
Vito M
VM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004195:Disease Models, Animal; D006977:Hypertension, Renal / Q000139:chemically induced / Q000503:physiopathology*; D007034:Hypothalamus, Posterior / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D009638:Norepinephrine / Q000096:biosynthesis / Q000378:metabolism; D018384:Oxidative Stress; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D019800:Phenol; D011092:Polyethylene Glycols / Q000494:pharmacology; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D003497:Cyclic N-Oxides; D007375:Interleukin-1; D007527:Isoenzymes; D021122:Protein Subunits; D013113:Spin Labels; D019800:Phenol; D011092:Polyethylene Glycols; D052248:Nitric Oxide Synthase Type I; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; D019255:NADPH Oxidases; C001803:tempol; D009638:Norepinephrine