Prostaglandin F_2α contracts coronary arteries smooth muscles under conditions of extra cellular and intracellular calcium depletion. In these conditions, nitrogen-oxide-containing vasodilators or natural EDRF(s) released by the kinins, substance P and bradykinin, from the endothelium relax strips of pig coronary arteries. This indicates that nitric oxide not only needs to lower cytosolic free calcium to relaxes the smooth muscles, but in addition another mechanism, independent of cytosolic calcium changes, is necessary to fully relax strips contracted by Prostaglandin F_2α.