© 1998 American Heart Association, Inc.
Original Contributions |
Autonomic Control of Vasomotion in the Porcine Coronary Circulation During Treadmill Exercise
Evidence for Feed-Forward ß-Adrenergic Control
From Experimental Cardiology, Thoraxcenter, Cardiovascular Research Institute COEUR, Erasmus University Rotterdam, Rotterdam, The Netherlands.
Correspondence to Dirk J. Duncker, MD, PhD, Experimental Cardiology, Thoraxcenter, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail Duncker{at}tch.fgg.eur.nl
Abstract—To date, no studies have
investigated coronary vasomotor control of myocardial
O2 delivery (MDO2) and its
modulation by the autonomic nervous system in the porcine heart during
treadmill exercise. We studied 8 chronically instrumented swine under
resting conditions and during graded treadmill exercise. Exercise up to
85% to 90% of maximum heart rate produced an increase in myocardial
O2 consumption (M
O2) from
163±16 µmol/min (mean±SE) at rest to 423±75 µmol/min
(P
0.05), which was paralleled by an increase in
MDO2, so that myocardial O2
extraction (79±1% at rest) and coronary venous O2
tension (cvPO2, 23.7±1.0 mm Hg at rest)
were maintained. ß-Adrenoceptor blockade blunted the exercise-induced
increase of MDO2 out of proportion compared
with the attenuation of the exercise-induced increase in
MO2, so that O2 extraction
rose from 78±1% at rest to 83±1% during exercise and
cvPO2 fell from 23.5±0.9 to 19.6±1.1
mm Hg (both P0.05). In contrast, 
-adrenoceptor
blockade, either in the absence or presence of ß-adrenoceptor
blockade, had no effect on myocardial O2 extraction or
cvPO2 at rest or during exercise. Muscarinic
receptor blockade resulted in a decreased O2 extraction and
an increase in cvPO2 at rest, an effect that
waned during exercise. The vasodilation produced by muscarinic receptor
blockade was likely due to an increased ß-adrenoceptor activity,
since combined muscarinic and ß-adrenoceptor blockade produced
similar changes in O2 extraction and
cvPO2, as did ß-adrenoceptor blockade alone.
In conclusion, in swine myocardium,
MO2 and MDO2 are
matched during exercise, which is the result of feed-forward
ß-adrenergic vasodilation in conjunction with minimal -adrenergic
vasoconstriction. ß-Adrenergic vasodilation is due to an increase in
sympathetic activity but may also be supported by withdrawal of
muscarinic receptor–mediated inhibition of ß-adrenergic
coronary vasodilation. The observation that
cvPO2 levels are maintained even during heavy
exercise suggests that a decrease in cvPO2 is
not essential for coronary vasodilation during exercise.
Key Words: coronary blood flow • exercise • myocardial O2 extraction • autonomic nervous system • myocardial O2 consumption
This article has been cited by other articles:
 |
|
 |
|
  O. Yamaguchi, T. Kaneshiro, S.-i. Saitoh, T. Ishibashi, Y. Maruyama, and Y. Takeishi Regulation of coronary vascular tone via redox modulation in the {alpha}1-adrenergic-angiotensin-endothelin axis of the myocardium Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H226 - H232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Duncker and R. J. Bache Regulation of Coronary Blood Flow During Exercise Physiol Rev, July 1, 2008; 88(3): 1009 - 1086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. J. de Beer, O. Sorop, D. A. Pijnappels, D. H. Dekkers, F. Boomsma, J. M. J. Lamers, D. J. Duncker, and D. Merkus Integrative control of coronary resistance vessel tone by endothelin and angiotensin II is altered in swine with a recent myocardial infarction Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2069 - H2077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Duncker and D. Merkus Exercise hyperaemia in the heart: the search for the dilator mechanism J. Physiol., September 15, 2007; 583(3): 847 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lynch, T.-C. Lee, J. A. Fallavollita, J. M. Canty Jr, and G. Suzuki Intracoronary Administration of AdvFGF-5 (Fibroblast Growth Factor-5) Ameliorates Left Ventricular Dysfunction and Prevents Myocyte Loss in Swine With Developing Collaterals and Ischemic Cardiomyopathy Circulation, September 11, 2007; 116(11_suppl): I-71 - I-76. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Kudej, Y.-T. Shen, A. P. Peppas, C.-H. Huang, W. Chen, L. Yan, D. E. Vatner, and S. F. Vatner Obligatory Role of Cardiac Nerves and {alpha}1-Adrenergic Receptors for the Second Window of Ischemic Preconditioning in Conscious Pigs Circ. Res., November 24, 2006; 99(11): 1270 - 1276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Merkus, O. Sorop, B. Houweling, B. A. Hoogteijling, and D. J. Duncker KCa+ channels contribute to exercise-induced coronary vasodilation in swine Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2090 - H2097. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Merkus, O. Sorop, B. Houweling, F. Boomsma, A. H. van den Meiracker, and D. J. Duncker NO and prostanoids blunt endothelin-mediated coronary vasoconstrictor influence in exercising swine Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2075 - H2081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Merkus, D. B. Haitsma, O. Sorop, F. Boomsma, V. J. de Beer, J. M. J. Lamers, P. D. Verdouw, and D. J. Duncker Coronary vasoconstrictor influence of angiotensin II is reduced in remodeled myocardium after myocardial infarction Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2082 - H2089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Tune Withdrawal of vasoconstrictor influences in local metabolic coronary vasodilation Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2044 - H2046. [Full Text] [PDF]
|
|
|
|
|
|
J. C. Ejike, L. S. L. Arakaki, D. A. Beard, W. A. Ciesielski, E. O. Feigl, and K. A. Schenkman Myocardial oxygenation and adenosine release in isolated guinea pig hearts during changes in contractility Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2062 - H2067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Merkus, A. K. Brzezinska, C. Zhang, S. Saito, and W. M. Chilian Cardiac myocytes control release of endothelin-1 in coronary vasculature Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2088 - H2092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Gorman, M. Farias III, K. N. Richmond, J. D. Tune, and E. O. Feigl Role of endothelin in {alpha}-adrenoceptor coronary vasoconstriction Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1937 - H1942. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Duncker, D. B. Haitsma, D. A. Liem, P. D. Verdouw, and D. Merkus Exercise unmasks autonomic dysfunction in swine with a recent myocardial infarction Cardiovasc Res, March 1, 2005; 65(4): 889 - 896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Merkus, B. Houweling, M. van Vliet, and D. J. Duncker Contribution of KATP+ channels to coronary vasomotor tone regulation is enhanced in exercising swine with a recent myocardial infarction Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1306 - H1313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Merkus, B. Houweling, A. H. van den Meiracker, F. Boomsma, and D. J. Duncker Contribution of endothelin to coronary vasomotor tone is abolished after myocardial infarction Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H871 - H880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. van der Velden, D. Merkus, B.R. Klarenbeek, A.T. James, N.M. Boontje, D.H.W. Dekkers, G.J.M. Stienen, J.M.J. Lamers, and D.J. Duncker Alterations in Myofilament Function Contribute to Left Ventricular Dysfunction in Pigs Early After Myocardial Infarction Circ. Res., November 26, 2004; 95(11): e85 - e95. [Abstract] [Full Text]
|
|
|
|
|
|
E. O. Feigl Berne's adenosine hypothesis of coronary blood flow control Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H1891 - H1894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W. Hein, C. Zhang, W. Wang, and L. Kuo Heterogeneous {beta}2-Adrenoceptor Expression and Dilation in Coronary Arterioles Across the Left Ventricular Wall Circulation, October 26, 2004; 110(17): 2708 - 2712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. C. Alders, A. B. J. Groeneveld, F. J. J. de Kanter, and J. H. G. M. van Beek Myocardial O2 consumption in porcine left ventricle is heterogeneously distributed in parallel to heterogeneous O2 delivery Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1353 - H1361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Tune, M. W. Gorman, and E. O. Feigl Matching coronary blood flow to myocardial oxygen consumption J Appl Physiol, July 1, 2004; 97(1): 404 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Merkus, B. Houweling, A. Zarbanoui, and D. J. Duncker Interaction between prostanoids and nitric oxide in regulation of systemic, pulmonary, and coronary vascular tone in exercising swine Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H1114 - H1123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Merkus, B. Houweling, A. Mirza, F. Boomsma, A. H van den Meiracker, and D. J Duncker Contribution of endothelin and its receptors to the regulation of vascular tone during exercise is different in the systemic, coronary and pulmonary circulation Cardiovasc Res, September 1, 2003; 59(3): 745 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Merkus, D. B. Haitsma, T.-Y. Fung, Y. J. Assen, P. D. Verdouw, and D. J. Duncker Coronary blood flow regulation in exercising swine involves parallel rather than redundant vasodilator pathways Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H424 - H433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Haitsma, D. Merkus, J. Vermeulen, P. D. Verdouw, and D. J. Duncker Nitric oxide production is maintained in exercising swine with chronic left ventricular dysfunction Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2198 - H2209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Tune, K. N. Richmond, M. W. Gorman, and E. O. Feigl Control of Coronary Blood Flow during Exercise Experimental Biology and Medicine, April 1, 2002; 227(4): 238 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B Haitsma, D. Bac, N. Raja, F. Boomsma, P. D Verdouw, and D. J Duncker Minimal impairment of myocardial blood flow responses to exercise in the remodeled left ventricle early after myocardial infarction, despite significant hemodynamic and neurohumoral alterations Cardiovasc Res, December 1, 2001; 52(3): 417 - 428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Hart, X. Bian, P. A. Gwirtz, S. Setty, and H. F. Downey Right ventricular oxygen supply/demand balance in exercising dogs Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H823 - H830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Duncker, H. H. Oei, F. Hu, R. Stubenitsky, and P. D. Verdouw Role of KATP+ channels in regulation of systemic, pulmonary, and coronary vasomotor tone in exercising swine Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H22 - H33. [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]
|
|
|
|
|
|
M. W. Gorman, J. D. Tune, K. N. Richmond, and E. O. Feigl Quantitative analysis of feedforward sympathetic coronary vasodilation in exercising dogs J Appl Physiol, November 1, 2000; 89(5): 1903 - 1911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. van Kats, D. J. Duncker, D. B. Haitsma, M. P. Schuijt, R. Niebuur, R. Stubenitsky, F. Boomsma, M. A. D. H. Schalekamp, P. D. Verdouw, and A. H. J. Danser Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Blockade Prevent Cardiac Remodeling in Pigs After Myocardial Infarction : Role of Tissue Angiotensin II Circulation, September 26, 2000; 102(13): 1556 - 1563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Duncker, R. Stubenitsky, P. A.L. Tonino, and P. D. Verdouw Nitric oxide contributes to the regulation of vasomotor tone but does not modulate O2-consumption in exercising swine Cardiovasc Res, September 1, 2000; 47(4): 738 - 748. [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]
|
|
|
|
|
|
J. Bartunek, W. Wijns, G. R. Heyndrickx, and B. de Bruyne Effects of Dobutamine on Coronary Stenosis Physiology and Morphology : Comparison With Intracoronary Adenosine Circulation, July 20, 1999; 100(3): 243 - 249. [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. J. Duncker, R. Stubenitsky, and P. D. Verdouw Role of adenosine in the regulation of coronary blood flow in swine at rest and during treadmill exercise Am J Physiol Heart Circ Physiol, November 1, 1998; 275(5): H1663 - H1672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Takamura, R. Parent, and M. Lavallee Enhanced contribution of NO to exercise-induced coronary responses after alpha -adrenergic receptor blockade Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H508 - H515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Haitsma, D. Merkus, J. Vermeulen, P. D. Verdouw, and D. J. Duncker Nitric oxide production is maintained in exercising swine with chronic left ventricular dysfunction Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2198 - H2209. [Abstract] [Full Text] [PDF]
|
|