Circulation. 2001;104:2305-2310
doi: 10.1161/hc4401.098293
doi: 10.1161/hc4401.098293
(Circulation. 2001;104:2305.)
© 2001 American Heart Association, Inc.
Clinical Investigations and Reports |
Influence of Nitric Oxide Synthase and Adrenergic Inhibition on Adenosine-Induced Myocardial Hyperemia
From the Center for Clinical Pharmacology (N.H.B.), the Department of Cardiology (M.B., T.T.N.), and the PET Center (F.H.), Aarhus University Hospital; the Center for Muscle Research, Copenhagen University (M.S.); and the Department of Pharmacology (M.J.M.), Aarhus University, Denmark.
Correspondence to Niels H. Buus, MD, PhD, Center for Clinical Pharmacology, Aarhus University Hospital, University Park 240, 8000 Aarhus C, Denmark. E-mail nhb{at}farm.au.dk
Background— Myocardial perfusion during adenosine-induced hyperemia is used both in clinical diagnosis of coronary heart disease and for scientific investigations of the myocardial microcirculation. The objective of this study was to clarify whether adenosine-induced hyperemia is dependent on endothelial NO production or is influenced by adrenergic mechanisms.
Methods and Results— In 12 healthy men, myocardial perfusion was measured with PET in 2 protocols performed in random order, each including 3 perfusion measurements. First, perfusion was measured at rest. Second, either saline or the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 4 mg/kg) was infused, and perfusion during adenosine-induced hyperemia was determined. Last, in both protocols, the 
-receptor blocker phentolamine was infused, and perfusion during adenosine-induced hyperemia was determined again. Resting perfusion was similar in the 2 protocols (0.69±0.14 and 0.66±0.18 mL · min-1 · g-1). L-NAME increased mean arterial blood pressure by 12±7 mm Hg (P<0.01) and reduced heart rate by 16±7 bpm (P<0.01). Adenosine-induced hyperemia (1.90±0.33 mL · min-1 · g-1) was attenuated by L-NAME (1.50±0.55 mL · min-1 · g-1, P<0.01). The addition of phentolamine had no effect on the adenosine-induced hyperemia (2.10±0.34 mL · min-1 · g-1, P=NS). In the presence of L-NAME, however, when the adenosine response was attenuated, phentolamine was able to increase hyperemic perfusion (2.05±0.44 mL · min-1 · g-1, P<0.05).
Conclusions— Inhibition of endogenous NO synthesis attenuates myocardial perfusion during adenosine-induced hyperemia, indicating that coronary vasodilation by adenosine is partly endothelium dependent. -Adrenergic blockade has no effect on adenosine-induced hyperemia unless NO synthesis is inhibited.
Key Words: adenosine • nitric oxide • perfusion • receptors, adrenergic, alpha • vasodilation
This article has been cited by other articles:
 |
|
 |
|
  N. Koivuviita, R. Tertti, M. Jarvisalo, M. Pietila, J. Hannukainen, J. Sundell, P. Nuutila, J. Knuuti, and K. Metsarinne Increased basal myocardial perfusion in patients with chronic kidney disease without symptomatic coronary artery disease Nephrol. Dial. Transplant., September 1, 2009; 24(9): 2773 - 2779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Shechter, S. Matetzky, M. Arad, M. S. Feinberg, and D. Freimark Vascular endothelial function predicts mortality risk in patients with advanced ischaemic chronic heart failure Eur J Heart Fail, June 1, 2009; 11(6): 588 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Meimoun, D. Malaquin, T. Benali, J. Boulanger, H. Zemir, and C. Tribouilloy Transient impairment of coronary flow reserve in tako-tsubo cardiomyopathy is related to left ventricular systolic parameters Eur J Echocardiogr, March 1, 2009; 10(2): 265 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. R. Schelbert Coronary circulatory function abnormalities in insulin resistance insights from positron emission tomography. J. Am. Coll. Cardiol., February 3, 2009; 53(5 Suppl): S3 - S8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Neglia, R. De Maria, S. Masi, M. Gallopin, P. Pisani, S. Pardini, A. Gavazzi, A. L'Abbate, and O. Parodi Effects of long-term treatment with carvedilol on myocardial blood flow in idiopathic dilated cardiomyopathy Heart, July 1, 2007; 93(7): 808 - 813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Morita, T. Tsukamoto, M. Naya, K. Noriyasu, M. Inubushi, T. Shiga, C. Katoh, Y. Kuge, H. Tsutsui, and N. Tamaki Smoking Cessation Normalizes Coronary Endothelial Vasomotor Response Assessed with 15O-Water and PET in Healthy Young Smokers J. Nucl. Med., December 1, 2006; 47(12): 1914 - 1920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Bitar, A. Lerman, M. W. Akhter, P. Hatamizadeh, M. Janmohamed, S. Khan, and U. Elkayam Variable response of conductance and resistance coronary arteries to endothelial stimulation in patients with heart failure due to nonischemic dilated cardiomyopathy. Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2006; 11(3): 197 - 202. [Abstract] [PDF]
|
|
|
|
 |
|
 R. Lautamaki, K.E. J. Airaksinen, M. Seppanen, J. Toikka, R. Harkonen, M. Luotolahti, R. Borra, J. Sundell, J. Knuuti, and P. Nuutila Insulin Improves Myocardial Blood Flow in Patients With Type 2 Diabetes and Coronary Artery Disease Diabetes, February 1, 2006; 55(2): 511 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Hagg, B. Wandt, G. Bergstrom, R. Volkmann, and L.-m. Gan Physical exercise capacity is associated with coronary and peripheral vascular function in healthy young adults Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1627 - H1634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. E. Vicario, L. Cirillo, G. Storto, T. Pellegrino, N. Ragone, L. Fontanella, M. Petretta, D. Bonaduce, and A. Cuocolo Influence of Risk Factors on Coronary Flow Reserve in Patients with 1-Vessel Coronary Artery Disease J. Nucl. Med., September 1, 2005; 46(9): 1438 - 1443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wikstrom, J. Gronros, G. Bergstrom, and L.-m. Gan Functional and Morphologic Imaging of Coronary Atherosclerosis in Living Mice Using High-Resolution Color Doppler Echocardiography and Ultrasound Biomicroscopy J. Am. Coll. Cardiol., August 16, 2005; 46(4): 720 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. O. Prior, M. J. Quinones, M. Hernandez-Pampaloni, A. D. Facta, T. H. Schindler, J. W. Sayre, W. A. Hsueh, and H. R. Schelbert Coronary Circulatory Dysfunction in Insulin Resistance, Impaired Glucose Tolerance, and Type 2 Diabetes Mellitus Circulation, May 10, 2005; 111(18): 2291 - 2298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Gewirtz, O. Rimoldi, T. Gnecchi-Ruscone, P. G. Camici, R. S. Bonser, P. A. Kaufmann, and T. F. Luscher Letter Regarding Article by Kaufmann et al, "Systemic Inhibition of Nitric Oxide Synthase Unmasks Neural Constraint of Maximal Myocardial Blood Flow in Humans" * Response Circulation, May 3, 2005; 111(17): e278 - e279. [Full Text] [PDF]
|
|
|
|
|
|
E. Nygard, K. F. Kofoed, J. Freiberg, S. Holm, J. Aldershvile, K. Eliasen, and H. Kelbaek Effects of High Thoracic Epidural Analgesia on Myocardial Blood Flow in Patients With Ischemic Heart Disease Circulation, May 3, 2005; 111(17): 2165 - 2170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. T. McMahon, J. Plutzky, E. Daher, T. Bhattacharyya, G. Grunberger, and M. F. DiCarli Effect of a Peroxisome Proliferator-Activated Receptor-{gamma} Agonist on Myocardial Blood Flow in Type 2 Diabetes Diabetes Care, May 1, 2005; 28(5): 1145 - 1150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Mishra, S. Dorbala, G. Logsetty, A. Hassan, T. Heinonen, H. R. Schelbert, M. F. Di Carli, and RAMPART Investigators Quantitative relation between hemodynamic changes during intravenous adenosine infusion and the magnitude of coronary hyperemia: Implications for myocardial perfusion imaging J. Am. Coll. Cardiol., February 15, 2005; 45(4): 553 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yoshinari, H. Yaoita, K. Maehara, and Y. Maruyama Different therapeutic responses to treadmill exercise of heart failure due to ischemia and infarction in rats Cardiovasc Res, February 1, 2005; 65(2): 457 - 468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fischer, S. Rossa, U. Landmesser, S. Spiekermann, N. Engberding, B. Hornig, and H. Drexler Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death Eur. Heart J., January 1, 2005; 26(1): 65 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Landmesser, N. Engberding, F. H. Bahlmann, A. Schaefer, A. Wiencke, A. Heineke, S. Spiekermann, D. Hilfiker-Kleiner, C. Templin, D. Kotlarz, et al. Statin-Induced Improvement of Endothelial Progenitor Cell Mobilization, Myocardial Neovascularization, Left Ventricular Function, and Survival After Experimental Myocardial Infarction Requires Endothelial Nitric Oxide Synthase Circulation, October 5, 2004; 110(14): 1933 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. H. Buus, M. Bottcher, C. G. Jorgensen, K. L. Christensen, K. Thygesen, T. T. Nielsen, and M. J. Mulvany Myocardial Perfusion During Long-Term Angiotensin-Converting Enzyme Inhibition or {beta}-Blockade in Patients With Essential Hypertension Hypertension, October 1, 2004; 44(4): 465 - 470. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Kaufmann, O. Rimoldi, T. Gnecchi-Ruscone, R. S. Bonser, T. F. Luscher, and P. G. Camici Systemic Inhibition of Nitric Oxide Synthase Unmasks Neural Constraint of Maximal Myocardial Blood Flow in Humans Circulation, September 14, 2004; 110(11): 1431 - 1436. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Janatuinen, J. Knuuti, J. O. Toikka, M. Ahotupa, P. Nuutila, T. Ronnemaa, and O. T. Raitakari Effect of Pravastatin on Low-Density Lipoprotein Oxidation and Myocardial Perfusion in Young Adults With Type 1 Diabetes Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1303 - 1308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Duvernoy, J. Martin, K. Briesmiester, A. Bargardi, O. Muzik, and L. Mosca Myocardial Blood Flow and Flow Reserve in Response to Hormone Therapy in Postmenopausal Women with Risk Factors for Coronary Disease J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2783 - 2788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tawakol, T. Omland, and M. A. Creager Direct effect of ethanol on human vascular function Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2468 - H2473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. H. Schindler, E. U. Nitzsche, M. Olschewski, I. Brink, M. Mix, J. Prior, A. Facta, M. Inubushi, H. Just, and H. R. Schelbert PET-Measured Responses of MBF to Cold Pressor Testing Correlate with Indices of Coronary Vasomotion on Quantitative Coronary Angiography J. Nucl. Med., March 1, 2004; 45(3): 419 - 428. [Abstract] [Full Text]
|
|
|
|
|
|
H Laine, J Sundell, P Nuutila, O T Raitakari, M Luotolahti, T Ronnemaa, T Elomaa, P Koskinen, and J Knuuti Insulin induced increase in coronary flow reserve is abolished by dexamethasone in young men with uncomplicated type 1 diabetes Heart, March 1, 2004; 90(3): 270 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.-L. Johansson, J. Sundell, K. Ekberg, C. Jonsson, M. Seppanen, O. Raitakari, M. Luotolahti, P. Nuutila, J. Wahren, and J. Knuuti C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E14 - E19. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. Janatuinen, J. Laakso, R. Laaksonen, R. Vesalainen, P. Nuutila, T. Lehtimaki, O. T Raitakari, and J. Knuuti Plasma asymmetric dimethylarginine modifies the effect of pravastatin on myocardial blood flow in young adults Vascular Medicine, August 1, 2003; 8(3): 185 - 189. [Abstract] [PDF]
|
|
|
|
|
|
U. Landmesser, S. Spiekermann, S. Dikalov, H. Tatge, R. Wilke, C. Kohler, D. G. Harrison, B. Hornig, and H. Drexler Vascular Oxidative Stress and Endothelial Dysfunction in Patients With Chronic Heart Failure: Role of Xanthine-Oxidase and Extracellular Superoxide Dismutase Circulation, December 10, 2002; 106(24): 3073 - 3078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Paiva, J. Laakso, H. Laine, R. Laaksonen, J. Knuuti, and O. T. Raitakari Plasma asymmetric dimethylarginine and hyperemic myocardial blood flow in young subjects with borderline hypertension or familial hypercholesterolemia J. Am. Coll. Cardiol., October 2, 2002; 40(7): 1241 - 1247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tawakol, M. A. Forgione, M. Stuehlinger, N. M. Alpert, J. P. Cooke, J. Loscalzo, A. J. Fischman, M. A. Creager, and H. Gewirtz Homocysteine impairs coronary microvascular dilator function in humans J. Am. Coll. Cardiol., September 18, 2002; 40(6): 1051 - 1058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Landmesser and H. Drexler Allopurinol and Endothelial Function in Heart Failure: Future or Fantasy? Circulation, July 9, 2002; 106(2): 173 - 175. [Full Text] [PDF]
|
|
|
|
|
|
J. Sundell, P. Nuutila, H. Laine, M. Luotolahti, K. Kalliokoski, O. Raitakari, and J. Knuuti Dose-Dependent Vasodilating Effects of Insulin on Adenosine-Stimulated Myocardial Blood Flow Diabetes, April 1, 2002; 51(4): 1125 - 1130. [Abstract] [Full Text] [PDF]
|
|