Hydrogen peroxide increases the activity of rat sympathetic preganglionic neurons in vivo and in vitro.
Reactive oxygen species (ROS) have been shown to modulate neuronal synaptic transmission and have also been implicated in cardiovascular diseases such as hypertension. The hypothesis that H(2)O(2) acting on sympathetic preganglionic neurons (SPNs) affects spinal sympathetic outflow was tested in the present study. H(2)O(2) was applied intrathecally via an implanted cannula to the T7-T9 segments of urethane-anesthetized rats. Blood pressure and heart rate were used as indices to evaluate the spinal sympathetic effects of H(2)O(2) in vivo. Intrathecal H(2)O(2) (100-1000 nmol) dose-dependently increased both the mean arterial pressure and heart rate. Reproducible pressor effects of H(2)O(2) (1000 nmol) applied consecutively at intervals of 30 min were observed. The pressor effects of intrathecal H(2)O(2) (1000 nmol) were attenuated by pretreatment with intrathecal administration of catalase (500 units), or N-acetyl-cysteine (1000 nmol). The pressor effects of intrathecal H(2)O(2) (1000 nmol) were also antagonized dose-dependently by prior intrathecal injection of AP-5 (DL-2-amino-5- phosphonovaleric acid, 10 and 30 nmol), or 6-cyano-7- nitroquinoxaline-2,3-dione, 10 and 30 nmol. In vitro electrophysiological study in spinal cord slices showed that superfusion of 1 mM H(2)O(2) for 3 min, which had no effect on membrane potential, caused an increase in amplitude of excitatory postsynaptic potentials in SPNs, but had little effect on that of inhibitory postsynaptic potentials. Taken together, these results demonstrated that oxidative stress in spinal cord may cause an increase in spinal sympathetic tone by acting on SPNs, which may contribute to ROS-induced cardiovascular dysfunction.
Lin
H H
HH
Department of Nursing, Tzu Chi College of Technology, 880 Section 2, Chien-Kuo Road, 970 Hualien, Taiwan.
Chen
C-H
CH
Hsieh
W-K
WK
Chiu
T H
TH
Lai
C-C
CC
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007278:Injections, Spinal; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000779:Anesthetics, Local; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D006861:Hydrogen Peroxide; D002374:Catalase; D014633:Valine; D003545:Cysteine