Mechanisms of Adenosine Triphosphate‐Mediated Vasodilation in Humans: Modest Role for Nitric Oxide and Vasodilating Prostaglandins

ATP is an endothelium‐dependent vasodilator and findings regarding the underlying signaling mechanisms are equivocal. We sought to determine the independent and interactive roles of nitric oxide (NO) and vasodilating prostaglandins (PGs) in ATP‐mediated vasodilation in young, healthy humans. In protocol 1 (n = 16), a dose‐response curve to intrabrachial infusion of ATP was performed before and after both single and combined inhibition of NO synthase (L‐NMMA) and cyclooxygenase (ketorolac). Forearm blood flow (FBF) was measured via venous occlusion plethysmography and forearm vascular conductance (FVC) was calculated. In this protocol, neither individual nor combined NO/PG inhibition had any effect on the vasodilatory response ( P = 0.22–0.99). In protocol 2 (n = 20), we determined whether any possible contribution of both NO and PGs to ATP vasodilation was greater at low vs high doses of ATP and whether inhibition during steady‐state infusion of the respective dose of ATP impacted the dilation. FBF in this protocol was measured via Doppler ultrasound. In Protocol 2, a significant effect of combined NO/PG inhibition was observed at both the low (ΔFVC = −31 ± 11%) and high (−25 ± 11%) dose. Collectively, our findings indicate a potential modest role for NO and PGs in the vasodilatory response to exogenous ATP in the human forearm, but this varies depending upon the method utilized for assessing FBF. Supported by HL102720