Renal sympathetic nerve responses to tempol in spontaneously hypertensive rats

Takatomi Shokoji, Akira Nishiyama, Yoshihide Fujisawa, Hirofumi Hitomi, Hideyasu Kiyomoto, Norihiro Takahashi, Shoji Kimura, Masakazu Kohno, Youichi Abe

Research output: Contribution to journalArticlepeer-review

128 Citations (Scopus)

Abstract

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/l 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.

Original languageEnglish
Pages (from-to)266-273
Number of pages8
JournalHypertension
Volume41
Issue number2
DOIs
Publication statusPublished - 2003 Feb 1

Keywords

  • Arterial pressure
  • Nervous system, sympathetic renal
  • Rats, inbred WKY
  • Rats, spontaneously hypertensive
  • Tempol

ASJC Scopus subject areas

  • Internal Medicine

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