title: Tempol lowers blood pressure and sympathetic nerve activity but not vascular O2- 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.
authors.affiliation: Department of Pharmacology and Toxicology and The Neuroscience Program, Michigan State University, East Lansing, Mich 48824, USA. xuhui2@msu.edu
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Fink
authors.forename: James J
authors.initials: JJ
authors.lastname: Galligan
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D003900:Desoxycorticosterone; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D012965:Sodium Chloride; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D014684:Venae Cavae / Q000187:drug effects / Q000378:metabolism
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; D013481:Superoxides; D011092:Polyethylene Glycols; D003900:Desoxycorticosterone; D012965:Sodium Chloride; C056165:acetovanillone; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; C001803:tempol