Published Online
on July 19, 2004

A more recent version of this article appeared on August 1, 2004

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Submitted on December 21, 2003
Revised on January 23, 2004

Effects of Local Administrations of Tempol and Diethyldithio-Carbamic on Peripheral Nerve Activity

Takatomi Shokoji; Yoshihide Fujisawa; Shoji Kimura; Matlubur Rahman; Hideyasu Kiyomoto; Keisuke Matsubara; Kumiko Moriwaki; Yasuharu Aki; Akira Miyatake; Masakazu Kohno; Youichi Abe; and Akira Nishiyama^*

From the Department of Pharmacology (T.S, S.K., M.R., Y.A., A.N.), Second Department of Internal Medicine (T.S., H.K., K.Matsubara, K.Moriwaki, Y.A., M.K.), and the Research Equipment Center (Y.F., A.M.), Kagawa Medical University, Japan.

^* To whom correspondence should be addressed. E-mail: akira{at}kms.ac.jp.

Abstract--We have recently shown that systemic administration of a superoxide dismutase mimetic, tempol, resulted in decreases in mean arterial pressure and heart rate along with a reduction in renal sympathetic nerve activity (RSNA). It has also been shown that these parameters are significantly increased by systemic administration of a superoxide dismutase inhibitor, diethyldithio-carbamic (DETC), indicating a potential role of reactive oxygen species in the regulation of RSNA. In this study, we examined the effects of local administrations of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) and DETC on RSNA in anesthetized rats. Either tempol or DETC was directly administered onto the renal sympathetic nerves located between the electrode and ganglion. Local application of tempol (10 µL, 0.17 to 1.7 mol/L, n=6) resulted in dose-dependent decreases in integrated RSNA (by -81±6% at 1.7 mol/L) without alterations in mean arterial pressure and heart rate. In contrast, DETC (10 µL, 0.17 to 1.7 mol/L, n=6) increased RSNA dose-dependently. The responses of RSNA to tempol and DETC were significantly greater in spontaneously hypertensive rats than in normotensive rats (n=6, respectively). Local application of sodium nitroprusside (1 mmol/L) or N^G-nitro-L-arginine methyl ester (0.11 mol/L) altered neither basal RSNA nor tempol-induced reductions in RSNA (n=6 and 5, respectively). A voltage-gated potassium channel blocker, 4-aminopyridine (0.1 mol/L), significantly decreased basal RSNA (by -81±1%) and completely prevented DETC-induced increases in RSNA (n=5). These results suggest that reactive oxygen species play a role in the regulation of peripheral sympathetic nerve activity, and that at least part of this mechanism is mediated through voltage-gated potassium channels.

Key words: nitric oxide • oxidative stress • potassium channels • rats, spontaneously hypertensive • sympathetic nervous system

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