Document Type
Article
Publication Date
9-2013
Publication Source
Circulation Research
Abstract
Rationale: Reactive hyperemia (RH) in the forearm circulation is an important marker of cardiovascular health, yet the underlying vasodilator signaling pathways are controversial and thus remain unclear.
Objective: We hypothesized that RH occurs via activation of inwardly rectifying potassium (KIR) channels and Na+/K+-ATPase and is largely independent of the combined production of the endothelial autocoids nitric oxide (NO) and prostaglandins in young healthy humans.
Methods and Results: In 24 (23±1 years) subjects, we performed RH trials by measuring forearm blood flow (FBF; venous occlusion plethysmography) after 5 minutes of arterial occlusion. In protocol 1, we studied 2 groups of 8 subjects and assessed RH in the following conditions. For group 1, we studied control (saline), KIR channel inhibition (BaCl2), combined inhibition of KIR channels and Na+/K+-ATPase (BaCl2 and ouabain, respectively), and combined inhibition of KIR channels, Na+/K+-ATPase, NO, and prostaglandins (BaCl2, ouabain, L-NMMA [NG-monomethyl-L-arginine] and ketorolac, respectively). Group 2 received ouabain rather than BaCl2 in the second trial. In protocol 2 (n=8), the following 3 RH trials were performed: control; L-NMMA plus ketorolac; and L-NMMA plus ketorolac plus BaCl2 plus ouabain. All infusions were intra-arterial (brachial). Compared with control, BaCl2 significantly reduced peak FBF (−50±6%; P2 (−61±3%) and ouabain (−44±12%) alone, and this effect was enhanced when combined (−87±4%), nearly abolishing RH. L-NMMA plus ketorolac did not impact total RH FBF before or after administration of BaCl2 plus ouabain.
Conclusions: Activation of KIR channels is the primary determinant of peak RH, whereas activation of both KIR channels and Na+/K+-ATPase explains nearly all of the total (AUC) RH in humans.
Inclusive pages
1023-1032
ISBN/ISSN
0009-7330
Document Version
Postprint
Publisher
American Heart Association
Volume
113
Issue
8
Peer Reviewed
yes
Keywords
blood flow regulation, ischemia, hyperpolarization, vasodilation
Sponsoring Agency
National Institutes of Health
eCommons Citation
Crecelius, Anne R.; Richards, Jennifer C.; Luckasen, Gary J.; Larson, Dennis G.; and Dinenno, Frank A., "Reactive Hyperemia Occurs Via Activation of Inwardly Rectifying Potassium Channels and Na+/K+-ATPase in Humans" (2013). Health and Sport Science Faculty Publications. 13.
https://ecommons.udayton.edu/hss_fac_pub/13
Included in
Cardiology Commons, Cardiovascular System Commons, Circulatory and Respiratory Physiology Commons
Comments
This is the peer-reviewed version of the following article:
Crecelius A.R., J.C. Richards, G.J. Luckasen, D.G. Larson and F.A. Dinenno. Reactive hyperemia occurs via activation of inwardly-rectifying potassium channels and Na+/K+-ATPase in humans. Circ Res. 113(8):1023-32. 2013.
The article available in the repository is the author's accepted manuscript; the version of record may contain minor differences that have come about in the copy editing and layout processes.