Caputi A P, Rossi F, Carney K, Brezenoff H E
J Pharmacol Exp Ther. 1980 Nov;215(2):309-16.
The effects of intracerebroventricular (i.c.v.) injection of physostigmine and hemicholinium-3 (HC-3) on reflex bradycardia and tachycardia have been studied in unanesthetized rats. The reflex increases and decreases in heart rate were elicited by i.v. injection of norepinephrine and sodium nitroprusside, respectively. Physostigmine (5-10 micrograms) increased basal mean arterial pressure (MAP), reduced basal heart rate (HR), enhanced the reflex bradycardia and reduced reflex tachycardia. Physostigmine did not modify either the pressor effect of norepinephrine, the depressor effect of sodium nitroprusside or the responsiveness of peripheral muscarinic receptors. Pretreatment (i.c.v.) with atropine (0.3 micrograms) completely abolished the effect of physostigmine on MAP, HR, reflex bradycardia and reflex tachycardia. Pretreatment (i.c.v.) with mecamylamine (50 micrograms) did not modify the effect of the cholinesterase inhibitor on MAP, HR and reflex tachycardia, but inverted its effect on reflex bradycardia. Injection of HC-3 (20 micrograms i.c.v.) did not modify MAP, but reduced HR and inhibited both reflex bradycardia and reflex tachycardia. The HC-3 bradycardic effect started within minutes and lasted for about 1 hr, while the depressor effect on the reflexes began only after 15 min and continued for several hours. In addition, i.c.v. pretreatment with HC-3 completely abolished all the effects of physostigmine on MAP, HR, reflex bradycardia and reflex tachycardia. These results suggest that brain acetylcholine has a modulatory effect on baroreceptor reflexes. This modulation operates through muscarinic receptors in reflex tachycardia and through both muscarinic and nicotinic receptors in reflex bradycardia.
在未麻醉的大鼠中，研究了脑室内注射毒扁豆碱和3-羟甲基氯化物（HC-3）对反射性心动过缓和心动过速的影响。分别通过静脉注射去甲肾上腺素和硝普钠引起心率的反射性增加和降低。毒扁豆碱（5-10微克）可提高基础平均动脉压（MAP），降低基础心率（HR），增强反射性心动过缓并降低反射性心动过速。毒扁豆碱既不改变去甲肾上腺素的升压作用、硝普钠的降压作用，也不改变外周毒蕈碱受体的反应性。预先脑室内注射阿托品（0.3微克）可完全消除毒扁豆碱对MAP、HR、反射性心动过缓和反射性心动过速的影响。预先脑室内注射美加明（50微克）不会改变胆碱酯酶抑制剂对MAP、HR和反射性心动过速的影响，但会反转其对反射性心动过缓的影响。注射HC-3（脑室内注射20微克）不会改变MAP，但会降低HR，并抑制反射性心动过缓和反射性心动过速。HC-3的心动过缓作用在数分钟内开始，持续约1小时，而对反射的降压作用仅在15分钟后开始，并持续数小时。此外，预先脑室内注射HC-3可完全消除毒扁豆碱对MAP、HR、反射性心动过缓和反射性心动过速的所有影响。这些结果表明，脑内乙酰胆碱对压力感受器反射具有调节作用。这种调节在反射性心动过速中通过毒蕈碱受体起作用，在反射性心动过缓中通过毒蕈碱受体和烟碱受体起作用。
