ATP-mediated Vasodilatation Occurs via Activation of Inwardly-Rectifying Potassium Channels in Humans

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Journal of Physiology


Circulating ATP possesses unique vasomotor properties in humans and has been hypothesized to play a role in vascular control under a variety of physiological conditions. However, the primary downstream signalling mechanisms underlying ATP-mediated vasodilatation remain unclear. The purpose of the present experiment was to determine whether ATP-mediated vasodilatation is independent of nitric oxide (NO) and prostaglandin (PG) synthesis and occurs primarily via the activation of Na+/K+-ATPase and inwardly rectifying potassium (KIR) channels in humans. In all protocols, young healthy adults were studied and forearm vascular conductance (FVC) was calculated from forearm blood flow (measured via venous occlusion plethysmography) and intra-arterial blood pressure to quantify local vasodilatation. Vasodilator responses (%ΔFVC) during intra-arterial ATP infusions were unchanged following combined inhibition of NO and PGs (n= 8; P > 0.05) whereas the responses to KCl were greater (P < 0.05). Combined infusion of ouabain (to inhibit Na+/K+-ATPase) and barium chloride (BaCl2; to inhibit KIR channels) abolished KCl-mediated vasodilatation (n= 6; %ΔFVC = 134 ± 13 vs. 4 ± 5%; P < 0.05), demonstrating effective blockade of direct vascular hyperpolarization. The vasodilator responses to three different doses of ATP were inhibited on average 56 ± 5% (n= 16) following combined ouabain plus BaCl2 infusion. In follow-up studies, BaCl2alone inhibited the vasodilator responses to ATP on average 51 ± 3% (n= 6), which was not different than that observed for combined ouabain plus BaCl2 administration. Our novel results indicate that the primary mechanism of ATP-mediated vasodilatation is vascular hyperpolarization via activation of KIR channels. These observations translate in vitro findings to humans in vivo and may help explain the unique vasomotor properties of intravascular ATP in the human circulation.

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Publisher citation Crecelius A.R., B.S. Kirby, G.J. Luckasen, D.G. Larson and F.A. Dinenno. ATP-mediated vasodilatation occurs via activation of inwardly-rectifying potassium channels in humans. J Physiol 590:5349-5359. 2012.

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