Conducted dilatation to ATP and K+ in rat skeletal muscle arterioles

Abstract

Aim: During exercise in humans, circulating levels of ATP and K⁺ increase at a time when blood flow increases to satisfy metabolic demand. Both molecules can activate arteriolar K⁺ channels to stimulate vasodilatation; here, it is established whether conducted dilatation is observed in a skeletal muscle bed.

Methods: Isolated and cannulated rat cremaster arterioles were used to assess both local and conducted responses. Agents were either added to the bath, focally pulse-ejected to the downstream end of arterioles, or in triple-cannulated arterioles, luminally perfused into the downstream branches to assess both local and conducted responses.

Results: The endothelium-dependent agonist ACh and the K_ATP channel opener levcromakalim each stimulated both local and conducted vasodilatation. Focal, bolus delivery of ATP (10 μm) or KCl (33 mm) to the outside of arterioles stimulated a biphasic vasomotor response: rapid vasoconstriction followed by dilatation as each washed away. At lower concentrations of KCl (19 mm), constriction was avoided, and instead, Ba²⁺ -sensitive local dilatation and conducted dilatation were both observed. Luminal perfusion of ATP avoided constriction and activated P2Y₁ receptors stimulating vasodilatation secondary to opening of K_Ca channels. In triple-cannulated arterioles, either ATP (10 μm) or K⁺ (15 mm) luminally perfused into daughter branches of a bifurcation stimulated local dilatation which conducted into the parent arteriole.

Conclusion: The recognized physiological autocrine and paracrine mediators ATP and K⁺ each act to evoke both local and conducted vasodilatation in rat cremaster arterioles. Therefore, in situations when circulating levels are raised, such as during exercise, these agents can act as important regulators of blood flow.

Keywords: KATP channel; KCa channel; KIR channel; conducted dilatation; cremaster; electrical coupling.