Influence of the CBI receptor antagonist, AM 251, on the regional haemodynamic effects of WIN-55212-2 or HU 210 in conscious rats

被引:28
作者
Gardiner, SM [1 ]
March, JE [1 ]
Kemp, PA [1 ]
Bennett, T [1 ]
机构
[1] Univ Nottingham, Sch Med, Queens Med Ctr, Sch Biomed Sci, Nottingham NG7 2UH, England
关键词
cannabinoids; HU; 210; WIN-55212-2; haemodynamics;
D O I
10.1038/sj.bjp.0704750
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 In conscious, freely-moving, male, Sprague-Dawley rats, the regional haemodynamic responses to the synthetic cannabinoids, WIN-55212-2 and HU 210, were compared. The possible involvement of cannabinoid, CB1-receptors, or beta(2)-adrenoceptors in the responses to WIN-55212-2 and HU 210 were investigated using the CB1-receptor antagonist, AM 251, or the beta(2)-adrenoceptor antagonist, ICI 118551, respectively. 2 Both WIN-55212-2 (150 mug kg(-1)) and HU 210 (100 mug kg(-1)) had pressor, renal, and mesenteric vasoconstrictor and hindquarters vasodilator actions, although the effects of HU 210 were much more sustained than those of WIN-55212-2. Lower doses of the cannabinoids (WIN-55212-2, 50 mug kg(-1), HU 210, 10 mug kg(-1)) had less consistent actions. 3 All the significant cardiovascular effects of WIN-55212-2 and HU 210 were antagonized by pretreatment with AM 251 (3 mg kg(-1)). Furthermore, pretreatment with the beta(2)-adrenoceptor antagonist, ICI 118551, inhibited the hindquarters vasodilator effects of WIN-55212-2 and of HU 210. 4 On the basis of the present findings, and our earlier work, it is suggested that, in conscious rats, the pressor and vasoconstrictor effects of HU 210 and WIN-55212-2 involve cannabinoid-receptor-mediated increases in sympathetic activity. The accompanying hindquarters vasodilator actions of these agonists are cannabinoid receptor-mediated and appear to involve beta(2)-adrenoceptors.
引用
收藏
页码:581 / 587
页数:7
相关论文
共 18 条
[1]   THE PHARMACOLOGY OF A BETA-2-SELECTIVE ADRENOCEPTOR ANTAGONIST (ICI-118,551) [J].
BILSKI, AJ ;
HALLIDAY, SE ;
FITZ GERALD, JD ;
WALE, JL .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1983, 5 (03) :430-437
[2]  
Gardiner S. M., 2002, British Journal of Pharmacology, V135, p202P
[3]  
Gardiner S. M., 2002, British Journal of Pharmacology, V135, p37P
[4]   REGIONAL HEMODYNAMIC-RESPONSES TO ADRENOCEPTOR ANTAGONISM IN CONSCIOUS RATS [J].
GARDINER, SM ;
BENNETT, T .
AMERICAN JOURNAL OF PHYSIOLOGY, 1988, 255 (04) :H813-H824
[5]   INVOLVEMENT OF BETA-2-ADRENOCEPTORS IN THE REGIONAL HEMODYNAMIC-RESPONSES TO BRADYKININ IN CONSCIOUS RATS [J].
GARDINER, SM ;
KEMP, PA ;
BENNETT, T ;
BOSE, C ;
FOULKES, R ;
HUGHES, B .
BRITISH JOURNAL OF PHARMACOLOGY, 1992, 105 (04) :839-848
[6]   Regional haemodynamic responses to the cannabinoid agonist, WIN 55212-2, in conscious, normotensive rats, and in hypertensive, transgenic rats [J].
Gardiner, SM ;
March, JE ;
Kemp, PA ;
Bennett, T .
BRITISH JOURNAL OF PHARMACOLOGY, 2001, 133 (03) :445-453
[7]   I-123-labeled AM251: A radioiodinated ligand which binds in vivo to mouse brain cannabinoid CB1 receptors [J].
Gatley, SJ ;
Gifford, AN ;
Volkow, ND ;
Lan, RX ;
Makriyannis, A .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1996, 307 (03) :331-338
[8]   Binding of the non-classical cannabinoid CP 55,940, and the diarylpyrazole AM251 to rodent brain cannabinoid receptors [J].
Gatley, SJ ;
Lan, RX ;
Pyatt, B ;
Gifford, AN ;
Volkow, ND ;
Makriyannis, A .
LIFE SCIENCES, 1997, 61 (14) :PL191-PL197
[9]   Modulation of peristalsis by cannabinoid CB1 ligands in the isolated guinea-pig ileum [J].
Izzo, AA ;
Mascolo, N ;
Tonini, M ;
Capasso, F .
BRITISH JOURNAL OF PHARMACOLOGY, 2000, 129 (05) :984-990
[10]  
Lake KD, 1997, J PHARMACOL EXP THER, V281, P1030