Shirasaka Tetsuro, Qiu De-Lai, Kannan Hiroshi, Takasaki Mayumi
Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Anesth Analg. 2007 Dec;105(6):1722-8, table of contents. doi: 10.1213/01.ane.0000286230.02948.77.
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.
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.
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.
These results indicate that icv administration of DEX decreases MAP by sympathetic inhibition and decreases HR by sympathetic inhibition and vagal stimulation.
α2受体在包括下丘脑在内的大脑中表达，其与自主神经系统控制有关。右美托咪定（DEX）全身给药对心血管反应的影响已为人熟知；然而，关于DEX中枢给药对清醒动物心血管反应的影响却知之甚少。在本研究中，我们探讨了脑室内（icv）注射DEX对清醒、未束缚大鼠心血管反应和交感神经活动的影响及其机制。
我们对清醒大鼠（n = 58）进行icv注射DEX（0.5、1和2微克/千克），并测量平均动脉血压（MAP）、心率（HR）和血浆儿茶酚胺。还对大鼠（n = 8）给予阿托品、普萘洛尔（n = 8）或六甲铵（n = 8），以评估迷走神经或交感神经传出活动对DEX诱导反应的影响。部分大鼠进行了颈动脉窦和主动脉神经去神经支配，以排除压力感受器反射的影响。
脑室内注射DEX剂量依赖性地降低MAP、HR和血浆去甲肾上腺素。大剂量DEX降低血浆肾上腺素。六甲铵或普萘洛尔可降低DEX诱导的MAP降低幅度。阿托品或普萘洛尔可降低HR降低幅度。六甲铵预处理大鼠中DEX诱导的MAP和HR降低幅度小于完整大鼠。窦神经和主动脉神经去神经支配大鼠中DEX诱导的MAP和HR降低幅度大于完整大鼠。
这些结果表明，icv注射DEX通过抑制交感神经降低MAP，并通过抑制交感神经和刺激迷走神经降低HR。
