Circulation Research, Vol 70, 1203-1216, Copyright © 1992 by American Heart Association

ARTICLES

Adrenergic blockade blunts adenosine concentration and coronary vasodilation during hypoxia

SC Herrmann and EO Feigl
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle 98195.

Myocardial hypoxia is thought to be an important stimulus for increasing interstitial adenosine concentration. The adenosine hypothesis of coronary control was investigated during steady-state hypoxia by making measurements of coronary venous and epicardial well adenosine concentrations in adrenergically intact dogs and in animals with alpha- and beta-receptor blockade. In the adrenergically intact group, hypoxia sufficient to lower coronary venous oxygen tension to 8 mm Hg increased coronary blood flow 243% from normoxic values. Both coronary venous and epicardial well adenosine concentrations were increased throughout the hypoxic period. In the adrenergically blocked group, hypoxia to a similar level of coronary venous oxygen tension produced an increase in coronary blood flow of only 75%, which was significantly less than in the adrenergically intact group (p less than 0.01). Coronary venous adenosine was only transiently elevated, and epicardial well adenosine was unchanged from control levels. In a separate group of alpha- and beta-receptor-blocked animals that received an infusion of L-homocysteine thiolactone during hypoxia, there was no difference in tissue S-adenosylhomocysteine levels compared with those of normoxic controls. It is concluded that much of the coronary vasodilation associated with systemic hypoxia is dependent on adrenergic activation and that adenosine may only play a role in sustained hypoxic vasodilation when adrenergic receptors are intact.

This article has been cited by other articles:

				A. Momen, V. Mascarenhas, A. Gahremanpour, Z. Gao, R. Moradkhan, A. Kunselman, J. P. Boehmer, L. I. Sinoway, and U. A. Leuenberger Coronary blood flow responses to physiological stress in humans Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H854 - H861. [Abstract] [Full Text] [PDF]

				T. Lauer, R. Loncar, and A. Deussen Tracer Adenosine: A Novel Myocardial Flow Marker J. Nucl. Med., April 1, 2003; 44(4): 641 - 648. [Abstract] [Full Text] [PDF]

				M. W. Gorman, J. D. Tune, K. N. Richmond, and E. O. Feigl Feedforward sympathetic coronary vasodilation in exercising dogs J Appl Physiol, November 1, 2000; 89(5): 1892 - 1902. [Abstract] [Full Text] [PDF]

				K. N. Richmond, J. D. Tune, M. W. Gorman, and E. O. Feigl Role of KATP+ channels and adenosine in the control of coronary blood flow during exercise J Appl Physiol, August 1, 2000; 89(2): 529 - 536. [Abstract] [Full Text] [PDF]

				J. D. Tune, K. N. Richmond, M. W. Gorman, and E. O. Feigl Role of Nitric Oxide and Adenosine in Control of Coronary Blood Flow in Exercising Dogs Circulation, June 27, 2000; 101(25): 2942 - 2948. [Abstract] [Full Text] [PDF]

				J. D. Tune, K. N. Richmond, M. W. Gorman, R. A. Olsson, and E. O. Feigl Adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H74 - H84. [Abstract] [Full Text] [PDF]

				K. N. Richmond, J. D. Tune, M. W. Gorman, and E. O. Feigl Role of K+ATP channels in local metabolic coronary vasodilation Am J Physiol Heart Circ Physiol, December 1, 1999; 277(6): H2115 - H2123. [Abstract] [Full Text] [PDF]

				T. Yada, K. N. Richmond, R. van Bibber, K. Kroll, and E. O. Feigl Role of adenosine in local metabolic coronary vasodilation Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1425 - H1433. [Abstract] [Full Text] [PDF]

				D. A. MacLean, L. I. Sinoway, and U. Leuenberger Systemic Hypoxia Elevates Skeletal Muscle Interstitial Adenosine Levels in Humans Circulation, November 10, 1998; 98(19): 1990 - 1992. [Abstract] [Full Text] [PDF]

				R. D. Lasley and R. M. Mentzer Jr. Dose-Dependent Effects of Adenosine on Interstitial Fluid Adenosine and Postischemic Function in the Isolated Rat Heart J. Pharmacol. Exp. Ther., August 1, 1998; 286(2): 806 - 811. [Abstract] [Full Text]

				G. S. Friedrichs, L. Chi, J. L. Park, and B. R. Lucchesi Adrenergic-dependent Effect of Adenosine-induced Ventricular Fibrillation in the Isolated Rabbit Heart Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1997; 2(4): 299 - 308. [Abstract] [PDF]

				D. W. Stepp, R. Van Bibber, K. Kroll, and E. O. Feigl Quantitative Relation Between Interstitial Adenosine Concentration and Coronary Blood Flow Circ. Res., September 1, 1996; 79(3): 601 - 610. [Abstract] [Full Text]

				T. Minamino, M. Kitakaze, K. Komamura, K. Node, H. Takeda, M. Inoue, M. Hori, and T. Kamada Activation of Protein Kinase C Increases Adenosine Production in the Hypoxic Canine Coronary Artery Through the Extracellular Pathway Arterioscler Thromb Vasc Biol, December 1, 1995; 15(12): 2298 - 2304. [Abstract] [Full Text]

				C. J. M. Kerkhof, P. J. W. Van Der Linden, and P. Sipkema Role of myocardium and endothelium in coronary vascular smooth muscle responses to hypoxia Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1296 - H1303. [Abstract] [Full Text] [PDF]