Potassium does not mimic EDHF in rat mesenteric arteries

K+ has been proposed to be EDHF in small arteries. We compared ACh‐stimulated, EDHF‐mediated dilatation/relaxation with raised [K+]o in rat mesenteric arteries. In pressurized arteries, ACh (10 μM) dilated all arteries. Raising [K+]o from 5.88 to 10.58 mM only dilated 30% of arteries. Ba2+ (30 μM) did not affect dilatation to ACh, but abolished 40% of dilatations to raised [K+]o. If [K+]o was lowered to 1.18 mM, restoring [K+]o to 5.88 mM produced dilatation which was depressed by Ba2+ or ouabain (1 mM). Combined application of Ba2+ and ouabain abolished dilatation. In 1.18 mM K+, dilatation to ACh was depressed by ouabain, but not by Ba2+. Combined application of Ba2+ and ouabain depressed dilatation further. Gap junction inhibitors (Gap‐27; 300 μM and 18‐α‐glycyrrhetinic acid; 100 μM) also depressed dilatation to ACh. In arteries mounted isometrically, ACh (1 μM) relaxed endothelium intact (+E), but not endothelium denuded (−E) arteries. Raising [K+]o from 5.9–10.9 mM failed to relax all arteries. When [K+]o was lowered to 1 mM, raising [K+]o to 6 mM produced relaxation. In −E arteries, relaxation was unaffected by Ba2+ but abolished by ouabain. In +E arteries, Ba2+ depressed and ouabain abolished relaxation. In +E arteries, with 1 mM K+, ACh relaxation was depressed by ouabain but not Ba2+. The combined application of Ba2+ and ouabain further depressed relaxation. In summary, both EDHF and raised [K+]o dilate/relax rat mesenteric arteries, though sensitivities to barium and ouabain differ. K+ may be a relaxing factor in this tissue, but its characteristics differ from EDHF. Gap junction inhibitors depress EDHF, implying an important role for myo‐endothelial gap junctions. British Journal of Pharmacology (2000) 130, 1174–1182; doi:10.1038/sj.bjp.0703412