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 mediated by an endothelium-derived hyperpolarizing factor (EDHF), the nature of which is as yet unknown. Experiments were performed to investigate whether the recently raised hypothesis that EDHF might be identified as the potassium ion, released by activation of endothelial K(Ca) channels and inducing relaxation by stimulation of Na+/K+-pump and the inward rectifier K+ conductance, might be valid for small rat gastric arteries. EDHF-induced relaxation (assessed as the nitro-L-arginine/indomethacin resistant component of acetylcholine-induced relaxation), but not nitroprus-side-induced relaxation is strongly inhibited in the presence of ouabain (0.5 mM)/Ba2+ (30 microM), ouabain being responsible for the greater part of the inhibition. This inhibition is reversible. Application of increasing concentrations of K+ elicits transient relaxations in some preparations, but in a greater part of the preparations, no or only small relaxations. In membrane potential measurements, it was found that increasing concentrations of extracellular K+ consistently depolarized smooth muscle cells, whereas acetylcholine elicits hyperpolarization. The K(Ca) channel openers NS 1619 and 1-EBIO elicit relaxation effects that are not diminished after removal of the endothelium and are not inhibited by ouabain/Ba2+. It is concluded that EDHF-mediated relaxation is sensitive to inhibition by ouabain/Ba2+, but that the relation of this inhibitory influence to an action of K+ as EDHF is uncertain.