Complex regional haemodynamic effects of anandamide in conscious rats

1 Experiments were carried out in conscious, chronically instrumented, male. Sprague-Dawley rats to delineate the regional haemodynamic effects of the putative endogenous cannabinoid, anandamide, (0.075-3 mg kg(-1)), and to dissect some of the mechanisms involved. 2 At all doses of anandamide, there was a significant, short-lived increase in mean arterial blood pressure associated with vasoconstriction in renal, mesenteric and hindquarters vascular beds. 3 The higher doses (2.5 and 3 mg kg(-1)), caused an initial, marked bradycardia accompanied, in some animals, by a fall in arterial blood pressure which preceded the hypertension. In addition, after the higher doses of anandamide, the hindquarters vasoconstriction was followed by vasodilatation. 4 Although some of the effects described above resembled those of 5-HT (25 mug kg(-1)), the bradycardia and hypotensive actions of the latter were abolished by the 5HT(3)-receptor antagonist, azasetron, whereas those of anandamide were generally unaffected. 5 None of the cardiovascular actions of anandamide were influenced by the CBI-receptor antagonist, AM 251, but its bradycardic effect was sensitive to atropine, and its hindquarters vasodilator action was suppressed by the beta(2)-adrenoceptor antagonist, ICI 118551. 6 The results differ, in several aspects, from those previously reported in anaesthetized animals, and underscore the important impact anaesthesia can have on responses to anandamide.