Systemically administered tempol reduces neuronal activity in paraventricular nucleus of hypothalamus and rostral ventrolateral medulla in rats

Shun-Guang Wei; Zhi-Hua Zhang; Yang Yu; Robert B Felder

doi:10.1097/HJH.0b013e3283200442

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Systemically administered tempol reduces neuronal activity in paraventricular nucleus of hypothalamus and rostral ventrolateral medulla in rats

Journal article

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Systemically administered tempol reduces neuronal activity in paraventricular nucleus of hypothalamus and rostral ventrolateral medulla in rats

Shun-Guang Wei, Zhi-Hua Zhang, Yang Yu and Robert B Felder

Journal of hypertension, Vol.27(3), pp.543-550

03/2009

DOI: 10.1097/HJH.0b013e3283200442

PMCID: PMC2867327

PMID: 19330914

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Abstract

Systemic administration of the superoxide scavenger tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) reduces blood pressure (BP), heart rate (HR) and sympathetic nerve activity in normotensive and hypertensive animals. The global nature of the depressor response to tempol suggests an inhibitory influence on cardiovascular presympathetic regions of the brain. This study examined several possible mechanisms for such an effect. In urethane anesthetized rats, as expected, intravenous tempol (120 microg mol/kg) reduced mean arterial pressure, HR and renal sympathetic nerve activity (RSNA). Concomitant central neuronal recordings revealed reduced spontaneous discharge (spikes/s) of neurons in the paraventricular nucleus of hypothalamus (from 2.9 +/- 0.4 to 0.8+/- 0.2) and the rostral ventrolateral medulla (RVLM; from 9.8 +/- 0.5 to 7.2 +/-0.4), two cardiovascular and autonomic regions of the brain. Baroreceptor-denervated rats had exaggerated sympathetic and cardiovascular responses. Pretreatment with the hydroxyl radical scavenger dimethyl sulfoxide (intravenous) attenuated the tempol-induced decreases in BP, HR and RSNA, but the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (intravenous or intracerebroventricular) had no effect. These findings suggest that systemically administered tempol acts upon neurons in paraventricular nucleus and RVLM to reduce BP, HR and RSNA, perhaps by reducing the influence of reactive oxygen species in those regions. The arterial baroreflex modulates the depressor responses to tempol. These central mechanisms must be considered in interpreting data from studies using systemically administered tempol to assess the role of reactive oxygen species in cardiovascular regulation.

Free Radical Scavengers - pharmacology

Injections, Intravenous

Sympathetic Nervous System - drug effects

Injections, Intraventricular

Dimethyl Sulfoxide - pharmacology

Male

Cyclic N-Oxides - administration & dosage

Spin Labels

NG-Nitroarginine Methyl Ester - administration & dosage

Dose-Response Relationship, Drug

Enzyme Inhibitors - administration & dosage

Heart Rate - drug effects

Neuroprotective Agents - pharmacology

Cyclic N-Oxides - pharmacology

Dimethyl Sulfoxide - administration & dosage

Blood Pressure - drug effects

Hypothalamus - drug effects

Neuroprotective Agents - administration & dosage

NG-Nitroarginine Methyl Ester - pharmacology

Medulla Oblongata - drug effects

Enzyme Inhibitors - pharmacology

Free Radical Scavengers - administration & dosage

Rats

Rats, Sprague-Dawley

Baroreflex - drug effects

Paraventricular Hypothalamic Nucleus - drug effects

Animals

Sympathetic Nervous System - surgery

Kidney - innervation

Nitric Oxide Synthase - metabolism

Infusions, Intravenous

Details

Title: Subtitle: Systemically administered tempol reduces neuronal activity in paraventricular nucleus of hypothalamus and rostral ventrolateral medulla in rats
Creators: Shun-Guang Wei - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Zhi-Hua Zhang
Yang Yu
Robert B Felder
Resource Type: Journal article
Publication Details: Journal of hypertension, Vol.27(3), pp.543-550
DOI: 10.1097/HJH.0b013e3283200442
PMID: 19330914
PMCID: PMC2867327
NLM abbreviation: J Hypertens
ISSN: 0263-6352
eISSN: 1473-5598
Publisher: England
Grant note: R01 HL063915 / NHLBI NIH HHS R01HL063915 / NHLBI NIH HHS R01HL073986 / NHLBI NIH HHS R01 HL073986 / NHLBI NIH HHS R01 HL073986-04 / NHLBI NIH HHS R01 HL063915-05 / NHLBI NIH HHS
Language: English
Date published: 03/2009
Academic Unit: Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984065395002771

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