The effects of centrally administered dexmedetomidine on cardiovascular and sympathetic function in conscious rats.
BACKGROUND
The alpha2-receptor is expressed in the brain, including the hypothalamus, where it is implicated in autonomic nervous system control. The effects of systemic administration of dexmedetomidine (DEX) on cardiovascular responses are well known; however, little is known about the effects of central administration of DEX on cardiovascular responses in conscious animals. In this study, we explored the effects and the mechanism of intracerebroventricularly (icv) administered DEX on cardiovascular responses and sympathetic nerve activity in conscious, unrestrained rats.


METHODS
We administered DEX (0.5, 1, and 2 microg/kg) icv and measured the mean arterial blood pressure (MAP), heart rate (HR), and plasma catecholamine in conscious rats (n = 58). Rats were also administered atropine (n = 8), propranolol (n = 8), or hexamethonium (n = 8) to assess the influence of vagal or sympathetic efferent activity in the DEX-induced responses. Some of the rats underwent carotid sinus and aortic nerve denervation to exclude the effect of the baroreceptor reflex.


RESULTS
Intracerebroventricular administration of DEX dose-dependently decreased MAP, HR, and plasma norepinephrine. Large dose of DEX decreased plasma epinephrine. The amplitude of MAP reduction induced by DEX was reduced by hexamethonium or propranolol. The amplitude of HR reduction was reduced by atropine or propranolol. The amplitude of MAP and HR reduction induced by DEX were smaller in hexamethonium-pretreatment rats than in intact ones. The amplitude of MAP and HR reduction induced by DEX were larger in sinus and aortic nerve denervation rats than in intact ones.


CONCLUSIONS
These results indicate that icv administration of DEX decreases MAP by sympathetic inhibition and decreases HR by sympathetic inhibition and vagal stimulation.
Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. shirasak@med.miyazaki-u.ac.jp
Tetsuro
T
Shirasaka
De-Lai
DL
Qiu
Hiroshi
H
Kannan
Mayumi
M
Takasaki
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects; D003243:Consciousness / Q000187:drug effects* / Q000502:physiology; D020927:Dexmedetomidine / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
D020927:Dexmedetomidine