K+ potentiates hyperosmolarity-induced vasorelaxations in rat skeletal muscle arterioles.

Several regulatory mechanisms have been proposed for the exercise hyperemia in skeletal muscles. Since different vasoactive factors might interact during the hyperemic response, we investigated the influence of elevated K(+) concentrations on hyperosmolarity (HO)-induced vasorelaxations. Small gluteal rat arteries were isolated and mounted in an organ bath for isometric tension recording. After precontraction with norepinephrine, 20 (S20), 40 (S40) or 60 mM (S60) sucrose was added in control conditions (5 mM K(+); K5) or in the presence of additional 3 (K8) or 5 mM (K10) K(+). Removal of the endothelium and the addition of ouabain, Ba(2+), iberiotoxin or 18-alpha glycyrrhetinic acid (alphaGA) were used to study the underlying mechanisms. Sucrose evoked significant concentration-dependent vasorelaxations (S20 15.62+/-1.61%; S40 26.47+/-1.71%; S60 43.66+/-2.50%), which were significantly increased on addition of 3 and 5 mM. After removal of the endothelium and in the presence of 5 x 10(-5) M alphaGA, the influence of K(+) was significantly blocked but not in the presence of 5 x 10(-5) M ouabain. The K(IR) channel inhibitor Ba(2+) and BK(Ca) channel inhibitor iberiotoxin totally abolished the potentiating effect. We conclude that K(+) significantly enhances the relaxing effect of HO in gluteal blood vessels. We hypothesize that K(+) may stimulate the endothelial K(IR) channels which elicits the release of a mediator of the BK(Ca) channels. This factor may be transferred through myo-endothelial gap-junctions to the smooth muscle cells where modulation of the BK(Ca) channels sensitizes the arteries for hyperosmolarity-induced relaxations.