Endogenous ATP and the Modulation of Sympathetic Vasoconstriction in Contracting Skeletal Muscle of Humans

Abstract

Exogenous ATP administration in humans can blunt sympathetic vasoconstriction in a dose‐dependent manner, similar to what occurs within contracting skeletal muscle (sympatholysis). Here, we tested the hypothesis that endogenous ATP increases during exercise and is associated with the magnitude of sympatholysis in humans (N = 9). We measured deep venous plasma [ATP] and forearm blood flow (Doppler ultrasound), and calculated ATP effluent (FBF x [ATP]) at rest and during 5 and 15% MVC rhythmic handgrip exercise (EX), before and during superimposed lower body negative pressure (LBNP; −40 mmHg). LBNP‐induced vasoconstriction was similar during 5% EX vs rest (ΔFBF = −25 ± 2% vs −33 ± 5%), whereas this was blunted during 15% EX (−4 ± 2%). LBNP at rest did not alter [ATP] nor ATP effluent. During the 5% EX trial, [ATP] and ATP effluent were 44 ± 7, 70 ± 9, and 50 ± 10 nmol/L and 1 ± 1, 7 ± 1, and 4 ± 1 nmol/min at rest, EX, and EX + LBNP, respectively. During the 15% EX trial, [ATP] and ATP effluent were 47 ± 5, 79 ± 11, and 71 ± 8 nmol/L and 1 ± 1, 16 ± 3, and 14 ± 1 nmol/min at rest, EX, and EX + LBNP, respectively. We conclude that endogenous ATP release is increased during exercise and must remain elevated during sympathetic stimulation in order to blunt the vasoconstrictor response. Further, the contribution of intravascular ATP to vascular control may ultimately be dependent on an interaction between blood flow and [ATP].Supported by NIH HL102720