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(Hypertension. 2007;50:360.)
© 2007 American Heart Association, Inc.

Original Articles

Sympathoexcitation by Oxidative Stress in the Brain Mediates Arterial Pressure Elevation in Salt-Sensitive Hypertension

From the Department of Nephrology and Endocrinology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.

Correspondence to Toshiro Fujita, Department of Nephrology and Endocrinology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. E-mail fujita-dis{at}h.u-tokyo.ac.jp

Central sympathoexcitation is involved in the pathogenesis of salt-sensitive hypertension. We have suggested that oxidative stress in the brain modulates the sympathetic regulation of arterial pressure. Thus, we investigated whether oxidative stress could mediate central sympathoexcitation in salt-sensitive hypertension. Five- to 6-week-old male Dahl salt-sensitive rats and salt-resistant rats were fed with a normal (0.3%) or high- (8%) salt diet for 4 weeks. In urethane-anesthetized and artificially ventilated rats, arterial pressure, renal sympathetic nerve activity, and heart rate decreased in a dose-dependent fashion, when 20 or 40 µmol of tempol, a membrane-permeable superoxide dismutase mimetic, was infused into the lateral cerebral ventricle. The same degree of reduction was noted in salt-sensitive and salt-resistant rats without salt loading. Salt loading significantly increased central tempol-induced reductions in arterial pressure (–29.1±4.8% versus –10.6±3.3% at 40 µmol; P<0.01), sympathetic nerve activity (–18.7±2.0% versus –7.1±1.8%; P<0.01), and heart rate (–10.7±2.8% versus –2.0±0.7%; P<0.05) in salt-sensitive rats but not in salt-resistant rats. Intracerebroventricular diphenyleneiodonium, a reduced nicotinamide-adenine dinucleotide phosphate oxidase inhibitor, also elicited significantly greater reduction in each parameter in salt-loaded salt-sensitive rats. Moreover, salt loading increased reduced nicotinamide-adenine dinucleotide phosphate–dependent superoxide production in the hypothalamus in salt-sensitive rats but not in salt-resistant rats. In addition, reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits p22^phox, p47^phox, and gp91^phox mRNA expression significantly increased in the hypothalamus of salt-loaded salt-sensitive rats. In conclusion, in salt-sensitive hypertension, increased oxidative stress in the brain, possibly via activation of reduced nicotinamide-adenine dinucleotide phosphate oxidase, may elevate arterial pressure through central sympathoexcitation.

Key Words: salt-sensitive hypertension • oxidative stress • brain • hypertension • salt • sympathetic nervous system • Dahl rat