Nitric oxide-independent effects of tempol on sympathetic nerve activity and blood pressure in DOCA-salt rats.
The role of sympathetic nerves and nitric oxide (NO) in tempol-induced cardiovascular responses was evaluated in urethane-anesthetized sham and deoxycorticosterone acetate (DOCA)-salt-treated (DOCA-salt) rats. Tempol (30-300 micromol/kg iv), a superoxide (O) scavenger, decreased renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) in DOCA-salt and sham rats. The antioxidants tiron and ascorbate did not alter MAP, HR, or RSNA in any rat. Tempol responses were unaffected after sham rats were treated with N(G)-nitro-L-arginine (L-NNA, 13 mg/kg). In DOCA-salt rats, L-NNA reduced tempol-induced depressor responses but not the inhibition of HR or RSNA. Tempol did not significantly decrease MAP, HR, or RSNA after hexamethonium (30 mg/kg iv) treatment in any rat. Dihydroethidine histochemistry revealed increased O levels in arteries and veins from DOCA-salt rats. Tempol treatment in vitro reduced O levels in arteries and veins from DOCA-salt rats. In conclusion, tempol-induced depressor responses are mediated largely by NO-independent sympathoinhibition in sham and DOCA-salt rats. There is an additional interaction between NO and tempol that contributes to depressor responses in DOCA-salt rats.
Department of Pharmacology and Toxicology and The Neuroscience Program, Michigan State University, East Lansing, Michigan 48824, USA.
Hui
H
Xu
Gregory D
GD
Fink
James J
JJ
Galligan
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D003900:Desoxycorticosterone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D018738:Hexamethonium / Q000494:pharmacology; D007202:Indicators and Reagents / Q000494:pharmacology; D007668:Kidney / Q000294:innervation; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012492:Salts / Q000494:pharmacology; D013113:Spin Labels; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism
D000959:Antihypertensive Agents; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D012492:Salts; D013113:Spin Labels; D019335:Nitroarginine; D009569:Nitric Oxide; D018738:Hexamethonium; D003900:Desoxycorticosterone; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D001205:Ascorbic Acid; D010100:Oxygen; C001803:tempol