ABSTRACT
The goal of the present study was to examine whether K + could be the endotheliumderived hyperpolarizing factor ( E D H F ) induced by substance P and bradykinin in porcine coronary arteries. A candidate E D H F molecule must be released by the en dothelial cells upon stimulation by the kinins. Both peptides evoked a large outward K +
current in cultured endothelial cells of porcine coronary arteries. A K + selective elec trode recorded an increase in K + concentration in the extracellular medium in the media of the coronary artery upon stimulation with kinins. The scavenging of the candidate E D H F molecule must abolish the E D H F effect. In coronary strips, the scavenging of K + with cryptate 2.2.2 abolished the endothelium-dependent relaxations produced by substance P and bradykinin which are resistant to nitro-L-arginine and indomethacin. Application of the exogenous candidate E D H F molecule must mimic the effect of E D H F on smooth muscle cells. The perifusion of a medium supplemented with K +
depolarized and contracted strips of coronary artery. However, the short application of exogenous K + ions hyperpolarized the smooth muscle cells. A mechanism of action that explains the effect of E D H F must be identified. Ouabain, an inhibitor of the N a + - K + ATPase, abolished the endothelium-dependent relaxations resistant to nitro-L-arginine and indomethacin without inhibiting the relaxation to endothelium-derived nitric oxide. These results are compatible with the concept that, in the porcine coronary artery, K + ions released by the endothelial cells are E D H F and that these ions hyperpolarize and hence relax the smooth muscle exclusively by activating the N a + - K + ATPase.
