K-DERIVED HYPERPOLARIZING FACTOR IN RAT ARTERIES( IS AN ENDOTHELIUM)

In arteries, muscarinic agonists such as acetylcholine release an unid entified, endothelium-derived hyperpolarizing factor (EDHF) which is n either prostacyclin nor nitric oxide(1-3). Here we show that EDHF-indu ced hyperpolarization of smooth muscle and relaxation of small resista nce arteries are inhibited by ouabain plus Ba2+; ouabain is a blocker of Na+/K+ ATPase(4) and Ba2+ blocks inwardly rectifying K+ channels(5) . Small increases in the amount of extracellular K+ mimic these effect s of EDHF in a ouabain- and Ba2+-sensitive, but endothelium-independen t, manner. Acetylcholine hyperpolarizes endothelial tells and increase s the K+ concentration in the myoendothelial space; these effects are abolished by charybdotoxin plus apamin. Hyperpolarization of smooth mu scle by EDHF is also abolished by this toxin combination, but these to xins do not affect the hyperpolarization of smooth muscle by added K+. These data show that EDHF is K+ that effluxes through charybdotoxin- and apamin-sensitive K+ channels on endothelial cells. The resulting i ncrease in myoendothelial K+ concentration hyperpolarizes and relaxes adjacent smooth-muscle cells by activating Ba2+-sensitive K+ channels and Na+/K+ ATPase, These results show that fluctuations in K+ levels o riginating within the blood vessel itself are important in regulating mammalian blood pressure and flow.