Nitric oxide-independent effects of tempol on sympathetic nerve activity and blood pressure in normotensive rats.
The role of the sympathetic nervous system in 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol)-induced cardiovascular responses in urethane-anesthetized, normotensive rats was evaluated. Tempol caused dose-dependent (30-300 micromol/kg iv) decreases in renal sympathetic nerve activity (RSNA), mean arterial blood pressure (MAP), and heart rate (HR). Similar responses were obtained after sinoaortic denervation and cervical vagotomy. These responses were not blocked following treatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine (2.6 mg x kg(-1) x min(-1) iv for 5 min) or the alpha2-adrenergic receptor antagonist idazoxan (0.3 mg/kg iv bolus). Idazoxan blocked the effects of clonidine (10 miccrog/kg iv) on HR, MAP, and RSNA. Hexamethonium (30 mg/kg iv) inhibited RSNA, and tempol did not decrease RSNA after hexamethonium. The effects of tempol on HR and MAP were reduced by hexamethonium. In conclusion, depressor responses caused by tempol are mediated, partly, by sympathoinhibition in urethane-anesthetized, normotensive rats. Nitric oxide does not contribute to this response, and the sympathoinhibitory effect of tempol is not mediated via alpha2-adrenergic receptors. Finally, tempol directly decreases HR, which may contribute to the MAP decrease.
Xu
H
H
Department of Pharmacology and Toxicology and Neuroscience Program, Michigan State University, East Lansing, Michigan 48824, USA.
Fink
G D
GD
Chen
A
A
Watts
S
S
Galligan
J J
JJ
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000502:physiology*
D009569:Nitric Oxide