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


RESULTS
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.


CONCLUSIONS
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.
Wei
Shun-Guang
SG
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Zhang
Zhi-Hua
ZH
Yu
Yang
Y
Felder
Robert B
RB