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-anesth etized, normotensive rats was evaluated. Tempol caused dose-dependent (30-3 00 mu mol/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 respons es were not blocked following treatment with the nitric oxide synthase inhi bitor N-G-nitro-L- arginine (2.6 mg.kg(-1).min(-1) iv for 5 min) or the alp ha2-adrenergic receptor antagonist idazoxan (0.3 mg/kg iv bolus). Idazoxan blocked the effects of clonidine (10 mug/kg iv) on HR, MAP, and RSNA. Hexam ethonium (30 mg/kg iv) inhibited RSNA, and tempol did not decrease RSNA aft er hexamethonium. The effects of tempol on HR and MAP were reduced by hexam ethonium. 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 sympathoinhibit ory effect of tempol is not mediated via alpha2-adrenergic receptors. Final ly, tempol directly decreases HR, which may contribute to the MAP decrease.