Central Tempol alters basal sympathetic nerve discharge and attenuates sympathetic excitation to central ANG II.
In the present study, we established dose-response relationships between central administration of 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol, a superoxide dismutase mimetic) and the level of renal sympathetic nerve discharge (SND) and tested the hypothesis that intracerebroventricular (icv) Tempol pretreatment would attenuate centrally mediated changes in SND produced by icv ANG II administration. Urethane-chloralose-anesthetized, baroreceptor-denervated, normotensive rats were used. We found that icv Tempol administration produced dose-dependent sympathoinhibitory, hypotensive, and bradycardic responses. Mean arterial pressure and SND values were significantly increased after icv ANG II (150 ng/kg) administration, and these responses were abrogated after icv pretreatment with Tempol (75 micromol/kg) or losartan. Brain superoxide levels tended to be higher in ANG II-treated rats compared with rats treated with Tempol and ANG II. Tempol pretreatment did not prevent increases in SND level that were produced by acute heat stress, which indicates specificity in the effect of Tempol in reducing sympathoexcitation. These results demonstrate that icv Tempol administration influences central sympathetic neural circuits in a dose-dependent manner and attenuates SND responses to central ANG II infusion.
Dept. of Anatomy and Physiology, Coles Hall 228, Kansas State Univ., 1600 Denison Ave., Manhattan, KS 66506, USA.
Ning
N
Lu
Bryan G
BG
Helwig
Richard J
RJ
Fels
Sujatha
S
Parimi
Michael J
MJ
Kenney
D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006358:Hot Temperature; D007276:Injections, Intraventricular; D019808:Losartan / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; D014662:Vasoconstrictor Agents; D013481:Superoxides; D000804:Angiotensin II; D019808:Losartan; C001803:tempol