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

Abstract

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, Ba²⁺, iberiotoxin or 18-α glycyrrhetinic acid (αGA) 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 5×10⁻⁵ M αGA, the influence of K⁺ was significantly blocked but not in the presence of 5×10⁻⁵ M ouabain. The K_IR channel inhibitor Ba²⁺ 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.