Mechanisms of ATP-mediated Vasodilation in Humans: Modest Role for Nitric Oxide and Prostaglandins

Author(s)

Anne R. Crecelius, University of DaytonFollow
Brett S. Kirby, Duke University Medical Center
Jennifer C. Richards, Colorado State University - Fort Collins
Leora J. Garcia, Colorado State University - Fort Collins
Wyatt F. Voyles, Medical Center of the Rockies Foundation
Dennis G. Larson, Medical Center of the Rockies Foundation
Gary J. Luckasen, Medical Center of the Rockies Foundation
Frank A. Dinenno, Colorado State University - Fort Collins

Document Type

Article

Publication Date

10-2011

Publication Source

American Journal of Physiology - Heart and Circulatory Physiology

Abstract

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 and determine whether any potential role was dependent on ATP dose or the timing of inhibition. In protocol 1 (n = 18), a dose-response curve to intrabrachial infusion of ATP was performed before and after both single and combined inhibition of NO synthase [NG-monomethyl-l-arginine (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 = 16), 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, infusion of low (n = 8)- and high-dose (n = 8) ATP for 5 min evoked a significant increase in FVC above baseline (low = 198 ± 24%; high = 706 ± 79%). Infusion of l-NMMA and ketorolac together reduced steady-state FVC during both low- and high-dose ATP (P < 0.05), and in a subsequent trial with continuous NO/PG blockade, the vasodilator response from baseline to 5 min of steady-state infusion was similarly reduced for both low (ΔFVC = −31 ± 11%)- and high-dose ATP (ΔFVC −25 ± 11%; P = 0.70 low vs. high dose). Collectively, our findings indicate a potential modest role for NO and PGs in the vasodilatory response to exogenous ATP in the human forearm that does not appear to be dose or timing dependent; however, this is dependent on the method for assessing forearm vascular responses. Importantly, the majority of ATP-mediated vasodilation is independent of these putative endothelium-dependent pathways in humans.

Inclusive pages

H1302-H1310

ISBN/ISSN

0363-6135

Comments

Article is also available through PubMed Central at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197353/

Publisher

American Physiological Society

Volume

301

Peer Reviewed

yes

Keywords

endothelium dependence, purine, adenosine triphosphate

Sponsoring Agency

National Heart, Lung, and Blood Institute

eCommons Citation

Crecelius, Anne R.; Kirby, Brett S.; Richards, Jennifer C.; Garcia, Leora J.; Voyles, Wyatt F.; Larson, Dennis G.; Luckasen, Gary J.; and Dinenno, Frank A., "Mechanisms of ATP-mediated Vasodilation in Humans: Modest Role for Nitric Oxide and Prostaglandins" (2011). Health and Sport Science Faculty Publications. 11.
https://ecommons.udayton.edu/hss_fac_pub/11