Potassium-induced release of endothelium-derived relaxing factor from canine femoral arteries

Abstract

Experiments were designed in a bioassay system to analyze the effect of elevated (from 5.9 mM to 7.5-45.9 mM) extracellular K+ concentration on the release of endothelium-derived relaxing factor. Segments of canine femoral artery with endothelium (donor segment) were mounted in an organ bath and perfused with modified Krebs-Ringer bicarbonate solution; the effluent from the donor segment was used to superfuse a canine coronary artery ring without endothelium (bioassay tissue). Elevation of perfusate K+ concentration by 1.6-15 mM by intraluminal infusion of potassium chloride upstream of the donor segment evoked further contractions of bioassay rings contracted with prostaglandin F(2α). In contrast, the bioassay rings progressively relaxed when increasing concentrations of potassium chloride (10-40 mM) were added extraluminally to the organ bath where the perfused segment was mounted. Extraluminal application of phenylephrine or prostaglandin F(2α) did not evoke relaxations in the bioassay ring. Removal of the endothelium from the donor segment or selective exposure of the segment (but not the bioassay ring) to Ca2+-deficient solution prevented the K+-induced relaxations. Treatment of the donor segment and the bioassay ring with inhibitors of known endogenous vasoactive substances (acetylcholine, norepinephrine, adenine nucleotides, and prostanoids) had no significant effect on the relaxation of the bioassay ring evoked by extraluminal application of potassium chloride. Simultaneous measurements of changes in isometric force in the donor segment and bioassay ring revealed that extraluminal elevation of K+ concentation relaxed the segments as well and that the relaxations could not be prevented by simultaneous intraluminal infusion of potassium chloride. Prolongation of the transit time between the donor segment and bioassay ring from 1 to 6 seconds depressed the relaxations of the bioassay tissue evoked by extraluminal elevation of K+ concentrations that could be prevented by superoxide dismutase (infused downstream of the donor segment). These findings indicate that K+ can stimulate the release of endothelium-derived relaxing factor from perfused canine femoral arteries but only when applied extraluminally. It is postulated that K+ triggers the release of a still unidentified mediator in the blood vessel wall that stimulates the release of the relaxing factor from the endothelial cells.