(Hypertension. 1999;33:1453-1457.)
© 1999 American Heart Association, Inc.
Scientific Contribution |
Intravascular Source of Adenosine During Forearm Ischemia in Humans
Implications for Reactive Hyperemia
From the Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tenn.
Correspondence to Italo Biaggioni, MD, Clinical Research Center, AA3228 MCN, Vanderbilt University, Nashville, TN 37232-2195. E-mail italo.biaggioni{at}mcmail.vanderbilt.edu
Abstract—It is believed that adenosine is released in ischemic tissues and contributes to reactive hyperemia. We tested this hypothesis in the human forearm using microdialysis to estimate interstitial and intravascular levels of adenosine and caffeine withdrawal to potentiate endogenous adenosine and determine its effect on reactive hyperemia. Forearm blood flow response to ischemia was measured by air plethysmography before and 60 hours after the last dose of caffeine (250 mg TID for 7 days, n=6). Forearm blood flow increased by 274±66% and 467±97% after 3 minutes of forearm ischemia, before and during caffeine withdrawal, respectively (P<0.05). Thus, caffeine withdrawal enhances reactive hyperemia. To determine the source of adenosine, we measured interstitial adenosine with the use of a microdialysis probe inserted into the flexor digitorum superficialis muscle of the forearm, and we measured intravascular adenosine with the use of a microdialysis probe inserted retrogradely into the medial cubital vein. Dialysate samples were collected at 15-minute intervals during resting, forearm ischemia, and recovery periods. Forearm ischemia failed to increase muscle dialysate concentrations of adenosine but did increase intravascular dialysate adenosine 2.1-fold, from 0.61±0.12 to 1.28±0.39 µmol/L (P<0.01, n=8). Intravascular dialysate concentrations of thromboxane B2 did not increase during ischemia, ruling out platelet aggregation as a source of adenosine. These results support the hypothesis that endogenous adenosine contributes to reactive hyperemia and indicate that the major source of adenosine in the human forearm is intravascular. We speculate that endothelial cells are the source of intravascular adenosine during ischemia.
Key Words: adenosine • ischemia • muscle • microdialysis
This article has been cited by other articles:
 |
|
 |
|
  M. S. Medow, I. Taneja, and J. M. Stewart Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H425 - H432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Loffler, J. C. Morote-Garcia, S. A. Eltzschig, I. R. Coe, and H. K. Eltzschig Physiological Roles of Vascular Nucleoside Transporters Arterioscler Thromb Vasc Biol, May 1, 2007; 27(5): 1004 - 1013. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Dupuis, A. Arsenault, B. Meloche, F. Harel, C. Staniloae, and J. Gregoire Quantitative hyperemic reactivity in opposed limbs during myocardial perfusion imaging: A new marker of coronary artery disease J. Am. Coll. Cardiol., October 6, 2004; 44(7): 1473 - 1477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Stewart, M. S. Medow, and L. D. Montgomery Local vascular responses affecting blood flow in postural tachycardia syndrome Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2749 - H2756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Feoktistov, A. E. Goldstein, S. Ryzhov, D. Zeng, L. Belardinelli, T. Voyno-Yasenetskaya, and I. Biaggioni Differential Expression of Adenosine Receptors in Human Endothelial Cells: Role of A2B Receptors in Angiogenic Factor Regulation Circ. Res., March 22, 2002; 90(5): 531 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F M Mo and H J Ballard The effect of systemic hypoxia on interstitial and blood adenosine, AMP, ADP and ATP in dog skeletal muscle J. Physiol., October 15, 2001; 536(2): 593 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Costa, N. J. Christensen, G. Farley, and I. Biaggioni NO modulates norepinephrine release in human skeletal muscle: implications for neural preconditioning Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2001; 280(5): R1494 - R1498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Costa, A. Diedrich, B. Johnson, P. Sulur, G. Farley, and I. Biaggioni Adenosine, a Metabolic Trigger of the Exercise Pressor Reflex in Humans Hypertension, March 1, 2001; 37(3): 917 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F L. Pasini, P. Capecchi, and T Di Perri Adenosine and chronic ischemia of the lower limbs Vascular Medicine, November 1, 2000; 5(4): 243 - 250. [Abstract] [PDF]
|
|
|
|
 |
|
 W.S. Waring, D.J. Webb, and S.R.J. Maxwell Uric acid as a risk factor for cardiovascular disease QJM, November 1, 2000; 93(11): 707 - 713. [Full Text] [PDF]
|
|
|
|
|
|
F. Costa, J. Heusinkveld, R. Ballog, S. Davis, and I. Biaggioni Estimation of Skeletal Muscle Interstitial Adenosine During Forearm Dynamic Exercise in Humans Hypertension, May 1, 2000; 35(5): 1124 - 1128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Feoktistov, A. E. Goldstein, S. Ryzhov, D. Zeng, L. Belardinelli, T. Voyno-Yasenetskaya, and I. Biaggioni Differential Expression of Adenosine Receptors in Human Endothelial Cells: Role of A2B Receptors in Angiogenic Factor Regulation Circ. Res., March 22, 2002; 90(5): 531 - 538. [Abstract] [Full Text] [PDF]
|
|