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 microg 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 CB(1)-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.