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

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.