Hyperosmolarity causes BK Ca-dependent vasodilatations in rat skeletal muscle arteries

The release of different metabolites during skeletal muscle contraction causes a pronounced increase in extracellular osmolarity (hyperosmolarity (HO)). HO has been considered as a possible mediator of the exercise hyperemia. In the present study, we investigated the vasodilatory effect of physiologically relevant increases in the extracellular osmolarity in isolated rat gluteal muscle arterioles. In addition, we analyzed the underlying mechanisms of the HO-induced vasodilatations.

Rat gluteal arteries were isolated and mounted in an organ bath for isometric tension recording. After precontraction with norepinephrine, 20, 40, or 60 mmol x L(-1) sucrose, mannitol, or urea was added in control conditions, after removal of the endothelium or in the presence of inhibitors.

Application of sucrose or mannitol induced large and fast concentration-dependent vasodilatations (up to 46.15% with 60 mmol x L(-1) sucrose). Removal of the vascular endothelium had no effect on this relaxation. Inhibition of the Na+/K+ pumps with ouabain, the Kir IR channels with Ba2+ and the K ATP channels with glibenclamide did not alter the HO-induced relaxations. Incubation with the KCa channel blockers charybdotoxin and apamin significantly inhibited sucrose-induced vasodilatations. In addition, application of the specific BK Ca channel blocker iberiotoxin significantly decreased the HO-induced vasodilatations.

The present study shows that an increase in the extracellular osmolarity elicits strong, fast, and long-lasting relaxations of rat skeletal muscle arterioles, suggesting an important role both at the onset and during the steady-state phase of an exercise bout. Vascular smooth muscle BK Ca channels seem to play a crucial role in the HO-induced vasorelaxations.