TY - JOUR
T1 - Renal sympathetic nerve responses to tempol in spontaneously hypertensive rats
AU - Shokoji, Takatomi
AU - Nishiyama, Akira
AU - Fujisawa, Yoshihide
AU - Hitomi, Hirofumi
AU - Kiyomoto, Hideyasu
AU - Takahashi, Norihiro
AU - Kimura, Shoji
AU - Kohno, Masakazu
AU - Abe, Youichi
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/2/1
Y1 - 2003/2/1
N2 - 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.
AB - 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.
KW - Arterial pressure
KW - Nervous system, sympathetic renal
KW - Rats, inbred WKY
KW - Rats, spontaneously hypertensive
KW - Tempol
UR - http://www.scopus.com/inward/record.url?scp=0037315837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037315837&partnerID=8YFLogxK
U2 - 10.1161/01.HYP.0000049621.85474.CF
DO - 10.1161/01.HYP.0000049621.85474.CF
M3 - Article
C2 - 12574093
AN - SCOPUS:0037315837
VL - 41
SP - 266
EP - 273
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 2
ER -