EDHF-mediated relaxation in rat gastric small arteries: Influence of ouabain/Ba2+ and relation to potassium ions

In several blood vessels, endothelium-dependent vasorelaxation is in part m ediated by an endothelium-derived hyperpolarizing factor (EDHF), the nature of which is as yet unknown. Experiments were performed to investigate whet her the recently raised hypothesis that EDHF might be identified as the pot assium ion, released by activation of endothelial K-Ca channels and inducin g relaxation by stimulation of Na+/K(+)pump and the inward rectifier K+ con ductance, might be valid for small rat gastric arteries. EDHF-induced relax ation (assessed as the nitro-L-arginine/indomethacin resistant component of acetylcholine-induced relaxation), but not nitroprusside-induced relaxatio n is strongly inhibited in the presence of ouabain (0.5 mM)/Ba2+ (30 mu M), ouabain being responsible for the greater part of the inhibition. This inh ibition is reversible. Application of increasing concentrations of K+ elici ts transient relaxations in some preparations, but in a greater part of the preparations, no or only small relaxations. In membrane potential measurem ents, it was found that increasing concentrations of extracellular K+ consi stently depolarized smooth muscle cells, whereas acetylcholine elicits hype rpolarization. The K-Ca channel openers NS 1619 and 1-EBIO elicit relaxatio n effects that are not diminished after removal of the endothelium and are not inhibited by ouabain/Ba2+. It is concluded that EDHF-mediated relaxatio n is sensitive to inhibition by ouabain/Ba2+ but that the relation of this inhibitory influence to an action of K+ as EDHF is uncertain.