In 1998, Edwards et al. proposed that potassium (K+) ions could be an endothelial-derived hyperpolarising factor (EDHF); however, the identity of EDHF remains controversial. Subsequent experiments in our laboratory have demonstrated that relaxation to K+ is not dependent on the presence of an intact endothelium and is ouabain sensitive (Brochet & Langton, 2001), indicating that smooth muscle Na+-K+-ATPase may be responsible for K+-induced relaxations. In the present study we have further investigated the effect of an increase of extracellular concentration of potassium ([K+]o) on the tone of rat isolated mesenteric arteries.
Male Wistar rats (200-250 g) were stunned and killed by cervical dislocation; third-order mesenteric arteries were dissected free and isometrically mounted for measurement of force. Arteries were contracted with phenylephrine (0.5-2 mM) to 70 % of the maximal response and relaxations measured against this contraction in the presence of N-nitro-L-arginine methyl ester (100 mM) and indomethacin (2.8 mM), inhibitors of NO synthase and cyclo-oxygenase, respectively. Raising [K+]o from 5.9 to 11.2 mM did not evoke relaxation of arteries with (+E, 106.7 ± 6.3% mean ± S.E.M., n = 7), or without, an endothelium (-E, 140.6 ± 7.7 %, n = 5). When [K+]o was initially lowered from 5.9 to 1.2 mM, restoring [K+]o back to 5.9 mM produced a relaxation (+E: 17.8 ± 4.2 %, n = 10). After lowering [K+]o from 5.9 to 1.2 mM for 3 min, increasing [K+]o to between 11.2 and 41.2 mM produced a transient relaxation, although concentrations higher than 41.2 mM evoked arterial contraction. Raising [K+]o from a range of concentrations, between 1.2 and 5.9 mM, to 13.8 mM resulted in a relaxation that was dependent on the initial [K+]o. These relaxations were abolished by 100 mM ouabain.
Arterial relaxations following lowered potassium may reflect a build-up of intracellular sodium during reduction of [K+]o and the subsequent over-run of the electrogenic Na+-K+-ATPase pumping when extracellular potassium is restored. Preventing an intracellular rise of sodium by replacing extracellular sodium with choline or TRIZMA abolished the relaxation to a rise in [K+]o from 1.2 to 13.8 mM (n = 12 and n = 6, respectively).
In summary, these data demonstrate that potassium-induced relaxation involves a ouabain-sensitive mechanism dependent on external sodium concentration, but independent of the endothelium.
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