ATP‐mediated vasodilation occurs via vascular hyperpolarization in humans

Abstract

ATP possesses unique vasomotor properties and has been hypothesized to contribute to the control of vascular tone under a variety of physiological conditions; however, in humans, the underlying vasomotor signaling mechanisms remain unknown. We sought to determine whether ATP‐mediated vasodilation occurs via vascular hyperpolarization in young healthy humans. In Protocol 1 (n=8), progressive doses of ATP and potassium chloride (KCl) were infused via brachial artery catheter. Forearm vascular conductance (FVC) was calculated from forearm blood flow (venous occlusion plethysmography) and intra‐arterial blood pressure to quantify local vasodilation. Vasodilatory responses (%ΔFVC) to ATP infusions were unchanged following combined inhibition of nitric oxide (NO) and prostaglandins (PGs; P>0.05) whereas the response to KCl was significantly greater (P<0.05). In Protocol 2 (n=21), infusion of both ouabain (to inhibit Na+/K+ ATPase) and barium chloride (BaCl2; to inhibit KIR channels) abolished KCl‐mediated vasodilation (%ΔFVC= 134±13 vs 4±5%; P<0.05) indicating effective inhibition of vasodilation mediated via hyperpolarization. On average, forearm vasodilation to 3 doses of ATP was inhibited ~60% following combined ouabain+BaCl2 infusion. Our novel results indicate that the majority of vasodilation in response to ATP occurs via vascular hyperpolarization in humans. Supported by HL102720