Tempol Lowers Blood Pressure and Sympathetic Nerve Activity But Not Vascular O ₂ ⁻ in DOCA-Salt Rats

Abstract

This study tested the hypothesis that depressor responses caused by tempol are not associated with reductions in vascular O2- levels in urethane-anesthetized deoxycorticosterone acetate (DOCA)-salt hypertensive rats. We compared the effects of intravenous (IV) administration of tempol, apocynin, superoxide dismutase-polyethylene glycol (PEG-SOD), and SOD on mean arterial blood pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). In DOCA-salt rats, tempol (30 to 300 micromol/kg) dose-dependently decreased RSNA, MAP, and HR. Tempol (300 micromol/kg) decreased MAP from 140+/-5 to 83+/-4 mm Hg (P<0.05). HR decreased from 435+/-15 to 390+/-12 bpm (P<0.05). RSNA was reduced by 54%+/-6% from baseline. However, in the same rats, tempol did not reduce dihydroethidium-induced fluorescent signals in the aorta and vena cava. Apocynin (200 micromol/kg) did not lower MAP (142+/-5 mm Hg versus 140+/-6 mm Hg) or HR (428+/-15 bpm versus 420+/-13 bpm) and apocynin did not potentiate depressor responses caused by tempol. PEG-SOD (10 000 U/kg, bolus or 5000 U/kg bolus followed by a 30-minutes infusion of 500 U/kg/min) or SOD (25 000 U/kg, bolus or 10 000 U/kg bolus followed by a 30-minutes infusion of 1000 U/kg per minute) did not alter MAP or HR. It is concluded that depressor responses and decreases in HR and RSNA caused by acute tempol treatment are caused by direct sympathetic nerve activity inhibition that is not accompanied by SOD-mimetic action in the aorta or vena cava.

Tempol Reduces Oxidative Stress, Improves Insulin Sensitivity, Decreases Renal Dopamine D1 Receptor Hyperphosphorylation, and Restores D1 Receptor–G-Protein Coupling and Function in Obese Zucker Rats

“…In addition, our in vitro studies showed that a similar concentration of SNP was required to inhibit NKA activity in lean and obese proximal tubules. Although the scavenging of superoxide radicals remains the central mechanism for its blood pressure-lowering mechanism, the effect of tempol on direct sympathetic nerve activity inhibition and heme-oxygenase system is also well documented (34,35). Recently, Yang et al (35) reported that tempol inhibits O 2 Ϫ -induced degradation of hypoxia-inducible factor-1␣.…”

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

“…23 However, Nakazono et al 24 showed that HB-SOD, which is a fusion protein consisting of human Cu/Zn-type SOD and a C-terminal basic peptide with high affinity for heparan sulfate on endothelial cells, significantly decreased blood pressure in SHR. From these observations, it seems likely that membrane permeability, a half-life, and/or distribution of these drugs or tempol might be critical for their effects on blood pressure and RSNA.…”

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

“…[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). 7 The results suggested that changes in K ϩ channel activity might contribute to sympatho-inhibition caused by tempol.…”

“…Sham operated and DOCA-salt hypertensive rats (male, 170 to 225 grams; Charles River Laboratories) were prepared as previously de-scribed. 2,6 Blood pressure was measured in conscious animals by tail-cuff plethysmography 4 weeks after DOCA implantation.…”

“…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 ).…”