Hypertension. 2003;41:266-273
Published online before print December 23, 2002, doi: 10.1161/01.HYP.0000049621.85474.CF
Published online before print December 23, 2002, doi: 10.1161/01.HYP.0000049621.85474.CF
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(Hypertension. 2003;41:266.)
© 2003 American Heart Association, Inc.
Scientific Contributions |
Renal Sympathetic Nerve Responses to Tempol in Spontaneously Hypertensive Rats
From the Second Department of Medicine (T.S., H.K., N.T., M.K.), the Department of Pharmacology (A.N., H.H., S.K., Y.A.), and Research Equipment Center (Y.F.), Kagawa Medical University, Kagawa, Japan.
Correspondence to Akira Nishiyama, MD, PhD, Department of Pharmacology, Kagawa Medical University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa 761-0793, Japan. E-mail akira{at}kms.ac.jp
Recent studies have implicated a contribution of oxidative stress to the development of hypertension. Studies were performed to determine the effects of the superoxide dismutase (SOD) mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol) on vascular superoxide production and renal sympathetic nerve activity (RSNA) in anesthetized Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Compared with WKY rats (n=6), SHR showed a doubled vascular superoxide production, which was normalized by treatment with Tempol (3 mmol/L, n=7). In WKY rats (n=6), Tempol (30 mg/kg IV) significantly decreased mean arterial pressure (MAP) from 108±5 to 88±6 mm Hg and HR from 304±9 to 282±6 beats/min. In SHR (n=6), Tempol significantly decreased MAP from 166±4 to 123±9 mm Hg and HR from 380±7 to 329±12 beats/min. Furthermore, Tempol significantly decreased RSNA in both WKY rats and SHR. On the basis of group comparisons, the percentage decreases in MAP (-28±4%), HR (-16±3%) and integrated RSNA (-63±6%) in SHR were significantly greater than in WKY rats (-17±3%, -9±2%, and -30±4%, respectively). In SHR, changes in integrated RSNA were highly correlated with changes in MAP (r=0.85, P<0.0001) during administration of Tempol (3, 10, and 30 mg/kg IV). In both WKY rats and SHR (n=4, respectively), intracerebroventricular injection of Tempol (300 µg/1 µL) did not alter MAP, HR, or RSNA. Intravenous administration of a SOD inhibitor, diethyldithio-carbamic acid (30 mg/kg), significantly increased MAP, HR, and integrated RSNA in both WKY rats and SHR (n=6, respectively). These results suggest that augmented superoxide production contributes to the development of hypertension through activation of the sympathetic nervous system.
Key Words: nervous system, sympathetic renal • rats, spontaneously hypertensive • rats, inbred WKY • Tempol • arterial pressure
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