Hyperosmolarity increases K+-induced vasodilations in rat skeletal muscle arterioles

Exercise hyperemia is mediated by a multitude of vasoactive metabolites released from the active skeletal muscle. Because several vasoactive factors might interact during the hyperemia response, we investigated the influence of hyperosmolarity (HO) on K(+)-induced relaxations.

Small gluteal rat arteries (diameter: 245 +/- 6 microm) were isolated and mounted in an organ bath for isometric tension recording. After precontraction with norepinephrine, 1, 2, or 3 mM K(+) was added in both control, moderate, or high hyperosmotic (30 mM (S30) or 60 mM sucrose (S60)) conditions. Endothelial removal and the addition of ouabain, Ba(2+), 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), or glibenclamide was used to study the underlying mechanisms.

The K(+)-induced relaxations were significantly (P < 0.001) increased in the presence of S30 and S60. Endothelial removal and the addition of glibenclamide or ouabain did not reduce the HO-induced increased sensitivity to K(+). The application of Ba abolished the influence of HO on the K(+)-induced relaxations. NPPB, a volume regulated anion channel (VRAC) blocker, mimicked the influence of HO by significantly (P < 0.05) increasing the K(+)-induced relaxations. Remarkably, the application of Ba(2+) abolished the sensitizing effect of NPPB on K(+)-induced relaxations.

HO increases the sensitivity of the rat gluteal skeletal muscle arteries to the vasodilating effect of K(+). It is hypothesized that HO inhibits VRAC causing smooth muscle hyperpolarization. This possibly sensitizes the K(ir)-channels that are known to be involved in the K-induced relaxations in this type of arteries.