In the present study, the mechanism of relaxant response of nitric oxide precursor, L-arginine, was investigated in goat isolated coronary artery. L-arginine (I mM) reversed the U-46619 (1 mu M)-induced contraction both in endothelium-intact and endothelium-denuded arterial ring preparations. L-arginine analogues, L-NAME, L-NNA and L-NMMA and the guanylyl cyclase inhibitor, methylene blue failed to attenuate the relaxant response of L-arginine. These observations negate the involvement of nitric oxide in mediating the relaxation by L-arginine. K-ATP channel blocker, glibenclamide (3 mu M), abolished the vasorelaxant responses Of L-arginine in endothelium-denuded preparations, thereby suggesting the involvement of K-ATP channels. Further, L-arginine also failed to induce relaxation of the coronary arterial rings constricted with K+ (80 mM)-PSS. Taken together, the results of the present study suggest that L-arginine relaxes goat isolated coronary artery through activation of K-ATP channels. (C) 2009 Elsevier B.V. All rights reserved