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

Abstract

AimDuring 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.MethodsIsolated 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.ResultsThe endothelium‐dependent agonist ACh and the KATP channel opener levcromakalim each stimulated both local and conducted vasodilatation. Focal, bolus delivery of ATP (10 μ m) 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 KC a channels. In triple‐cannulated arterioles, either ATP (10 μ m) or K+ (15 mm) luminally perfused into daughter branches of a bifurcation stimulated local dilatation which conducted into the parent arteriole.ConclusionThe 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.

Endothelial‐smooth muscle cell interactions in the regulation of vascular tone in skeletal muscle

“…When studied in isolation and under luminal pressure, ACh stimulates an increase in EC Ca 2+ , hyperpolarization and dilation of rat cremaster arterioles, a response underpinned by opening all three subtypes of Ca 2+ ‐activated K + (K Ca ) channels: small (S), intermediate (I), and large (B) conductance, sensitive to apamin, TRAM‐34, and iberiotoxin, respectively . In cremaster arterioles, both SK Ca and IK Ca channels are present in ECs, whereas BK Ca channels are present in at least SMCs .…”

“…The concentration of extracellular ATP increases when erythrocytes are made hypoxic, and can act at EC purinergic P2X and P2Y receptors to stimulate dilation . When luminally applied to arterioles, ATP stimulates both local and conducted dilation both in vivo and in isolated cremaster arterioles .…”

“…The concentration of extracellular ATP increases when erythrocytes are made hypoxic, and can act at EC purinergic P2X and P2Y receptors to stimulate dilation . When luminally applied to arterioles, ATP stimulates both local and conducted dilation both in vivo and in isolated cremaster arterioles . In this context ATP can act via G q/11 ‐coupled P2Y 1 receptors although other receptors likely also play a role; and if broken down to adenosine, can potentially act at adenosine receptors .…”

“…It relies on the passage of current through gap junctions, often including a role for myoendothelial gap junctions, using the endothelium as the conduit, reviewed in (Figure ), and does not require further opening of K + channels at the upstream sites. In most cases conducted dilation is not altered in the presence of a nitric oxide synthase inhibitor …”

Vascular KATP channels mitigate severe muscle O2 delivery-utilization mismatch during contractions in chronic heart failure rats

“…O 2 supply) via K + efflux-induced hyperpolarization. Accordingly, recent studies in isolated skeletal muscle arterioles demonstrate that the K ATP channel opener levcromakalim evokes both local and conducted vasodilation (Dora, 2017). K ATP channel inhibition in vivo exaggerates baroreflex-mediated vasoconstriction (Keller et al, 2004) whereas its activation attenuates α-adrenergic vasoconstriction (Nakai and Ichihara, 1994; Tateishi and Faber, 1995).…”