Effect of mivazerol, a alpha-agonist, on striatal norepinephrine concentration during transient forebrain ischemia in rats.
BACKGROUND
We have previously reported that mivazerol, a alpha(2)-agonist, possibly provides neuroprotection against transient forebrain ischemia in rats. This study was designed to investigate the ability of mivazerol to attenuate ischemia-induced increase in striatal norepinephrine concentration after transient forebrain ischemia in rats.


METHODS
Male Sprague-Dawley rats, anesthetized with halothane, were assigned to one of three groups (n=10 each); control (C, normal saline 1 ml/kg), mivazerol 20 microg/kg (M20), and 40 microg/kg (M40) groups. Monitored variables included temporal muscle temperature (maintained at 37.5+/-0.1 degrees C), electroencephalogram, systolic/diastolic blood pressure, heart rate, arterial blood gases, and blood glucose concentrations. Thirty minutes after subcutaneous drug administration, forebrain ischemia was induced with hemorrhagic hypotension (systolic arterial pressure: 40-50 mmHg) and bilateral carotid artery occlusion for 10 min, and then the brain was reperfused. Norepinephrine concentration in the interstitial fluids in the striatum was analyzed using in vivo microdialysis in combination with high-performance liquid chromatography.


RESULTS
Ischemia resulted in a prompt increase in norepinephrine concentrations in the striatum in all groups. However, there were no significant differences in norepinephrine concentrations in the striatum between the three groups at any period.


CONCLUSIONS
Our results indicate that mivazerol did not attenuate ischemia-induced increase in striatal norepinephrine concentration. This suggests that the possible neuroprotective property of mivazerol is not related to inhibition of norepinephrine release in the brain.
Kimura
T
T
Department of Anesthesia and Intensive Care Medicine, Akita University School of Medicine, Akita, Japan. kimtetsu@doc.med.akita-u.ac.jp
Sato
K
K
Nishikawa
T
T
Tobe
Y
Y
Masaki
Y
Y
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D007093:Imidazoles / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D016548:Prosencephalon; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D018696:Neuroprotective Agents; D012965:Sodium Chloride; C087969:mivazerol; D009638:Norepinephrine