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1 The e ects of the endocannabinoid, anandamide, and its metabolically stable analogue, methanandamide, on induced tone were examined in sheep coronary artery rings in vitro. 2 In endothelium-intact rings precontracted to the thromboxane A 2 mimetic, U46619, anandamide (0.01 ± 30 mM) induced slowly developing concentration-dependent relaxations (pEC 50 [negative log of EC 50 ]=6.1+0.1; R max [maximum response]=81+4%). Endothelium denudation caused a 10 fold rightward shift of the anandamide concentration-relaxation curve without modifying R max . Methanandamide was without e ect on U46619-induced tone. 3 The anandamide-induced relaxation was una ected by the cannabinoid receptor antagonist, SR 141716A (3 mM), the vanilloid receptor antagonist, capsazepine (3 and 10 mM) or the nitric oxide synthase inhibitor, L-NAME (100 mM). 4 The cyclo-oxygenase inhibitor, indomethacin (3 and 10 mM) and the anandamide amidohydrolase inhibitor, PMSF (70 and 200 mM), markedly attenuated the anandamide response. The anandamide transport inhibitor, AM 404 (10 and 30 mM), shifted the anandamide concentration-response curve to the right. 5 Precontraction of endothelium-intact rings with 25 mM KCl attenuated the anandamide-induced relaxations (R max =7+7%), as did K + channel blockade with tetraethylammonium (TEA; 3 mM) or iberiotoxin (100 nM). Blockade of small conductance, Ca 2+ -activated K + channels, delayed recti®er K + channels, K ATP channels or inward recti®er K + channels was without e ect. 6 These data suggest that the relaxant e ects of anandamide in sheep coronary arteries are mediated in part via the endothelium and result from the cellular uptake and conversion of anandamide to a vasodilatory prostanoid. This, in turn, causes vasorelaxation, in part, by opening potassium channels.

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