Nitric oxide-independent effects of tempol on sympathetic nerve activity and blood pressure in normotensive rats

Abstract

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.

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

“…11 Furthermore, sinoaortic denervation and cervical vagotomy do not alter the responses of RSNA and systemic hemodynamics to tempol. 10 Although these findings suggest that the sympathoinhibitory effects of tempol are mediated through mechanisms that are independent of the central nervous system and do not require intact baroreceptor reflex pathways, the action sites of tempol on the sympathetic nervous system have not yet been clarified.…”

“…5,6 Several in vitro studies also demonstrated that tempol and DETC alter acetylcholine-induced vasodilation under some experimental conditions, [7][8][9] suggesting that ROS production contributes to altered control of vasomotor tone. Xu et al 10 reported for the first time that tempol had the ability to reduce renal sympathetic activity (RSNA) in anesthetized Sprague-Dawley (SD) rats. We have also shown that in anesthetized Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR), systemic administration of tempol results in decreases in mean arterial pressure (MAP) and heart rate (HR) along with a significant reduction in RSNA.…”

“…However, Xu et al 10,14 reported that the responses of RSNA to systemic administration of tempol were not affected following treatment with an NO synthase inhibitor. Thus, the mechanisms responsible for tempol-induced reduction in RSNA are still not clear.…”

Activation of Vascular BK Channel by Tempol in DOCA-Salt Hypertensive Rats

“…1 4-Hydroxy 2,2,6,6,-tetramethyl piperidine 1-oxyl (tempol), a superoxide dismutase (SOD) mimetic, lowers blood pressure in normotensive and hypertensive rats by multiple mechanisms. [2][3][4][5] Acute tempol treatment of normotensive, DOCA-salt and spontaneously hypertensive rats (SHRs) inhibits sympathetic nerve activity and this effect is not prevented by nitric oxide synthase (NOS) inhibition. [2][3][4][5][6] Local application of tempol onto renal sympathetic nerves decreased nerve activity without changing blood pressure (BP) or heart rate (HR).…”

“…2,4,6 An ileal loop was drawn out and fixed to a silatic chamber perfused with Krebs solution (37°C). The Krebs solution contains (mmol/L): NaCl 118, KCl 4.7, MgCl 2 1.1, NaH 2 PO 4 1.2, CaCl 2 2.5, NaHCO 3 25, glucose 11, equilibrated with compressed air (5% CO 2 -21% O 2 -74% N 2 ).…”