6-Hydroxydopamine 투여 흰쥐의 혈압에 미치는 Clonidine의 영향

Abstract

It has been reported that the hypotensive action of clonidine is α_(2)-adrenoceptor agonistic effect. From clinical experiences it has been known that clonidine is antagonized by tricyclic antidepressants. Thus this experiment was set up to investigate the hypotensiva mechanism of clonidine and the interaction of clonidine with desipramine by using 6-OHDA which has the effect of sympathetomy. As is reported that the neonatal 6-OHDA administration prevents the development of various forms of experimental hypertension, the investigation was made with seven week's treatment of DOCA-Saline, to see the role of adrenergic neuron on the development of hypertension. The summarized results are as follows; 1. Administration of clonidine 100㎍/kg reduced the blood pressure(B.P.) of rats remarkably. And the case of pretreatment with desipramine 600㎍/kg, the hypotensive effect of clonidine was significantly reduced in comparison with the clonidine treatment alone. (P<0.001) 2. In the case of neonatally 6-OHDA treated rats, the hypotensive effect ef clonidine was not shown. And to be compared with the clonidine effect on normal rats, there is significant difference. (P<0.001) 3. In the case of normal rats, DOCA-Saline treated group showed 29.95% higher B.P. than that of untreated group. But in the case of neonatally 6-OHDA administered rats, DOCA-Saline treated group showed just 5.4% higher B.P. than that of untreated group.;중추성 혈압 강하제 clonidine은 α_(2)-adrenoceptor에 대한 효능이 있다고 보고된 바 있으며 삼환계 항우울약과 병용투여시 혈압 강하작용이 감소된다는 임상적 보고가 있어, sympathectomy 효과가 있는 6-hydroxydopamine(이하 6-OHDA)을 사용해 clonldin의 혈압 강하작용 기전과 desipramine과의 상호작용을 검토하였고, 신생쥐에 6-OHDA을 투여했을 때 실험적 고혈압의 유발이 억제된다는 보고에 따라 7주간 deoxycorticosterone acetate(이하 DOCA)와 saline을 처치하여 고혈압의 발생에 미치는 교감신경의 역할을 검토하여 다음과 같은 결론을 얻었다. 1. 정상쥐에 clonidine 100 μg/kg투여로 현저한 혈압 강하작용이 나타났으며 desipramine으로 전처리 후 clondine을 투여한 군은 단독 투여군에 비해 혈압 강하 효과가 매우 유의적으로 감소되었다. (P<0.001) 2. 신생시에 6-OHDA을 투여한 군에 대해 clonidine의 혈압 강하효과는 거의 나타나지 않았으며, 정상쥐에 clonidine 투여시의 혈압변화와 비교할 때 그 차이는 매우 유의적이었다. (P<0.001) 3. 정상쥐에 DOCA-saline 처치시, 처치하지 않은 군에 비해 29.95% 높은 혈압을 나타냈고, 신생시 6-OHDA 투여쥐에 DOCA-saline 처치시는, 처치하지 않은 군에 비해 볼과 5.4% 높은 혈압을 나타냈다.