An evaluation of potassium ions as endothelium-derived hyperpolarizing factor in porcine coronary arteries

1 In the rat hepatic artery, the endothelium-derived hyperpolarizing factor (EDHF) was identified as potassium. Potassium hyperpolarizes the smooth mu scles by gating inward rectified potassium channels and by activating the s odium-potassium adenosine triphosphatase (Na+-K(+)ATPase). Our goal was to examine whether potassium could explain the EDHF in porcine coronary arteri es. 2 On coronary strips, the inhibition of calcium-dependent potassium channel s with 100 nM apamin plus 100 muM charibdotoxin inhibited the endothelium-d ependent relaxations, produced by 10 nM substance P and 300 nM bradykinin a nd resistant to nitro-L-arginine and indomethacin. 3 The scavenging of potassium with 2 mM Kryptofix 2.2.2 abolished the endo thelium-dependent relaxations produced by the kinins and resistant to nitro -l-arginine and indomethacin. 4 Forty muM 18 alpha glycyrrethinic acid or 50 muM palmitoleic acid, both u ncoupling agents, did not inhibit these kinin relaxations. Therefore, EDHF does not result from an electrotonic spreading of an endothelial hyperpolar ization. 5 Barium (0.3 nM) did not inhibit the kinin relaxations resistant to nitro- l-arginine and indomethacin. Therefore, EDHF does not result from the activ ation of inward rectified potassium channels. 6 Five hundred nM ouabain abolished the endothelium-dependent relaxations r esistant to nitro-L-arginine and indomethacin without inhibiting the endoth elium-derived NO relaxation. 7 The perifusion of a medium supplemented with potassium depolarized and co ntracted a coronary strip; however, the short application of potassium hype rpolarized the smooth muscles. 8 These results are compatible with the concept that, in porcine coronary a rtery, the EDHF is potassium released by the endothelial cells and that thi s ion hyperpolarizes and relaxes the smooth muscles by activating the Na+-K (+)ATPase.