Sympatholytic effect of intravascular ATP is independent of Nitric Oxide, prostaglandins, Na+/K+-ATPase, and KIR channels in humans

Exercise and intravascular ATP elicit vasodilatation that is dependent on activation of inwardly rectifying potassium (KIR) channels, with a modest reliance on nitric oxide (NO) and prostaglandin (PG) synthesis.  Both exercise and intravascular ATP attenuate sympathetic α-adrenergic vasoconstriction (sympatholysis). However, KIR channels, NO, PGs and Na+/K+-ATPase activity are not obligatory to observe sympatholysis during exercise. To further determine similarities between exercise and intravascular ATP, we tested the hypothesis that inhibition of KIR channels, NO and PG synthesis, and Na+/K+-ATPase, would not alter the ability of ATP to blunt α1-adrenergic vasoconstriction. In healthy subjects, we measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (FVC) to intra-arterial infusion of phenylephrine (PE; α1-agonist) during ATP or control vasodilator infusion, before and after KIR channel inhibition alone (barium chloride; n = 7; Protocol 1); NO (L-NMMA) and PG (ketorolac) inhibition alone, or combined NO, PGs, Na+/K+-ATPase (ouabain) and KIR channel inhibition (n = 6; Protocol 2). ATP attenuated PE-mediated vasoconstriction relative to adenosine (ADO) and sodium nitroprusside (SNP) (PE-mediated ΔFVC: ATP: −16 ± 2; ADO:−38 ± 6; SNP: −59 ± 6%; P   0.05 vs. control). These findings demonstrate that intravascular ATP modulates α1-adrenergic vasoconstriction via pathways independent of KIR channels, NO, PGs, and Na+/K+-ATPase in humans, consistent with a role for endothelium-derived hyperpolarization in functional sympatholysis. This article is protected by copyright. All rights reserved