IMIDAZOLINE RECEPTORS - A NEW CONCEPT IN CENTRAL REGULATION OF THE ARTERIAL BLOOD-PRESSURE

被引：50

作者：

BOUSQUET, P

FELDMAN, J

TIBIRICA, E

BRICCA, G

GRENEY, H

DONTENWILL, M

STUTZMANN, J

BELCOURT, A

机构：

[1] Institut de Pharmacologie, CNRS URA 589, Strasbourg, 67000

来源：

AMERICAN JOURNAL OF HYPERTENSION | 1992年 / 5卷 / 04期

关键词：

Central nervous system; Hypotension; Imidazoline preferring receptors; Locus coeru- leus; Nucleus reticularis lateralis; Rilmenidine;

D O I：

10.1093/ajh/5.4.47S

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

Clonidine-like antihypertensive substances bind to nonadrenergic imidazoline specific sites within the nucleus reticularis lateralis (NRL), their medullary privileged site of action. Rilmenidine, a new central antihypertensive agent, was tested in the anesthetized rabbit. For the same hypotensive effect, cumulative doses given intracisternally proved 50 times more active than of those given systemically. Idazoxan, an alpha-2-adrenergic antagonist structurally related to the imidazolines, given centrally as pretreatment proved more potent in preventing the hypotensive effects than the same molar dose of yohimbine. When injected within the NRL area of the anesthetized rabbit, rilmenidine, like clonidine, always exhibited a hypotensive effect. The influence of clonidine and rilmenidine upon the NRL noradrenergic neurons involved in the blood pressure regulation, and upon those of the locus coeruleus (LC) involved in the sedative effect was studied by differential voltammetry. It was observed that rilmenidine was two times more selective than clonidine in inhibiting the NRL, as opposed to LC, neuronal activity. In addition, binding experiments of tritiated clonidine to human cortical and NRL membrane preparations showed that rilmenidine, as compared to clonidine, has a two to three times higher selectivity for the imidazoline receptors. In conclusion, we are now able to discriminate between the mechanism of the hypotensive effect of imidazoline-like drugs and that of their sedative action. Rilmenidine is the first example of an hypotensive drug more selective for imidazoline preferring receptors than for classical alpha-2-adrenoceptors.

引用

页码：S47 / S50

页数：4

共 21 条

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