Clonidine의 아드레날린 수용체에 미치는 영향에 관한 실험적 연구

Abstract

Biphasic pressure change and decrease in the heart rate are well known cardiovascular effects of clonidine. Extensive pharmacologic studies on the mecha· nism and site of action of this antihypertensive agent have been done by many researchers since 1966. However the results of the studies have been variable. Clonidine has been reported to lower blood pressure and heart rate in animals and man, by a central action from the beginning of the study. It is recently established that in addition to its central action, clonidine also inhibits the release of the transmitter from the peripheral sympathetic nerve endings and that this effect is mediated by presynaptic inhibitory «-adrenoceptors. The purpose of this study is to review the cardiovascular effects of clonidine and to define the relationship between mechanism of action of clonidine and adrenoceptors. The intravenous injection of clonidine (1. 0~50. 0 pg/kg) into rabbits caused bradycardia and biphasic change in arterial blood pressure, characterized by an initial transient pressor response followed by a sustained fall. The initial pressor response was prolonged and often potentiated by pretreatment with ganglion blocking agent, hexamethonium(5mg/kg), but depressor response and bradycardic effect were not blocked by it. The changes of cardiovascular effects of clonidine after pretreatment with adrenoceptor blocking agents such as propranolol, phentolamine and yohimbine were observed. The pressor effect was blocked by at and a,-receptor blocker, phentolamine, but not by a,-receptor blocker, yohimbine or ganglion blocker, hexamethonium. Hexamethonium inhibited the depressor effect of clonidine, and additional phentolamine or yohimbine inhibited it further. The bradycardic effect was also affected by hexamethonium, phentolamine and yohimbine respectively. The results are summerized as follows: 1. The initial pressor effect of clonidine results from stimulation of a-adrenergic receptors, especially at-receptors located on peripheral vascular wall. 2. The depressor effect of clonidine involves not only central inhibition of an adrenergic mechanism but also peripheral action mediating a-adrenergic receptors of the a, type. 3. The bradycardic effect of clonidine also results from activation of both central and peripheral aadrenergic receptors of the a2 type.