Imai Y, Nolan P L, Johnston C I
Clin Exp Hypertens A. 1986;8(2):239-58. doi: 10.3109/10641968609074774.
The centrally mediated cardiovascular changes induced by clonidine were studied in conscious rats. Clonidine administered intracerebroventricularly (i.c.v.), and intravenously (i.v.) caused hypotension following an initial pressor response. I.v. clonidine caused significant greater hypotension than i.c.v. clonidine (30 micrograms/kg; p less than 0.05). With the 30 micrograms/kg i.c.v. dose, a tachycardia was observed in all rats following initial transient bradycardia. No tachycardia was observed when clonidine was administered i.v. Propranolol (3 mg/kg i.v.) did not modify the cardiovascular actions of i.c.v. clonidine except initial pressure response. While combined treatment with propranolol (3 mg/kg i.v.) and atropine (1 mg/kg i.v.) abolished both the bradycardic and tachycardic actions of i.c.v. clonidine (30 micrograms/kg), but did not modulate the hypotensive action. Yohimbine (30 micrograms/kg i.c.v.) converted the hypotension induced by i.c.v. clonidine (30 micrograms/kg) to hypertension, attenuated the bradycardia but did not modulate the tachycardia. The same dose of i.c.v. yohimbine attenuated the hypotensive effect of i.v. clonidine (30 micrograms/kg) but did not affect the initial pressor response. Prazosin (30 micrograms/kg i.c.v.) did not modulate either phase of the heart rate response to i.c.v. clonidine. These results provide evidence of centrally mediated pressor and tachycardic actions of clonidine in conscious rats. The tachycardia appears to be mediated through the inhibition of parasympathetic tone and is not dependent on alpha-adrenoceptor mechanism. In conscious rats the opposing influence of centrally mediated pressor and depressor actions may result in the apparently low hypotensive potency of i.c.v. clonidine.
在清醒大鼠中研究了可乐定引起的中枢介导的心血管变化。脑室内（i.c.v.）和静脉内（i.v.）给予可乐定后，最初出现升压反应，随后导致低血压。静脉注射可乐定引起的低血压明显大于脑室内注射可乐定（30微克/千克；p<0.05）。给予30微克/千克脑室内注射剂量时，所有大鼠在最初短暂的心动过缓后均出现心动过速。静脉注射可乐定时未观察到心动过速。普萘洛尔（3毫克/千克静脉注射）除了最初的血压反应外，未改变脑室内注射可乐定的心血管作用。虽然普萘洛尔（3毫克/千克静脉注射）和阿托品（1毫克/千克静脉注射）联合治疗消除了脑室内注射可乐定（30微克/千克）的心动过缓和心动过速作用，但未调节低血压作用。育亨宾（30微克/千克脑室内注射）将脑室内注射可乐定（30微克/千克）引起的低血压转变为高血压，减弱了心动过缓，但未调节心动过速。相同剂量的脑室内注射育亨宾减弱了静脉注射可乐定（30微克/千克）的低血压作用，但未影响最初的升压反应。哌唑嗪（30微克/千克脑室内注射）未调节脑室内注射可乐定时心率反应的任何阶段。这些结果提供了可乐定在清醒大鼠中具有中枢介导的升压和心动过速作用的证据。心动过速似乎是通过抑制副交感神经张力介导的，并且不依赖于α-肾上腺素能受体机制。在清醒大鼠中，中枢介导的升压和降压作用的相反影响可能导致脑室内注射可乐定的明显低降压效力。
