Renal sympathetic nerve responses to tempol in spontaneously hypertensive rats.
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 micro g/1 micro L) 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.
Shokoji
Takatomi
T
Second Department of Medicine, Kagawa Medical University, Kita-Gun, Kagawa, Japan.
Nishiyama
Akira
A
Fujisawa
Yoshihide
Y
Hitomi
Hirofumi
H
Kiyomoto
Hideyasu
H
Takahashi
Norihiro
N
Kimura
Shoji
S
Kohno
Masakazu
M
Abe
Youichi
Y
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000494:pharmacology*; D004050:Ditiocarb / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D007668:Kidney / Q000294:innervation; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology
D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; D013481:Superoxides; D004050:Ditiocarb; C001803:tempol