(Circulation. 1996;93:646-651.)
© 1996 American Heart Association, Inc.
Articles |
Enhanced Coronary Vasoconstriction to Endothelin-BReceptor Activation in Experimental Congestive Heart Failure
From the Division of Cardiovascular Diseases and Internal Medicine, Department of Internal Medicine and Physiology, Mayo Clinic/Foundation, Rochester, Minn.
Correspondence to Amir Lerman, MD, Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
Background Endothelin (ET), a coronary vasoconstrictor, mediates its activity through the specific receptors ET-A and ET-B, which may demonstrate different activity under pathophysiological conditions. Thoracic inferior vena cava constriction (TIVCC) is an experimental model of congestive heart failure that is characterized by a decrease in cardiac output and an increase in circulating ET concentrations. The present study was designed to test the hypothesis that experimental heart failure altered coronary vascular responsiveness to ET-A– and ET-B–receptor stimulation in vivo.
Methods and Results ET-1 was infused at a rate of 2 ng/kg per minute into the left circumflex coronary artery in normal dogs (n=5) and in dogs subjected to TIVCC (TIVCC dogs, n=6). Similarly, sarafotoxin, an ET-B–receptor agonist, was infused at the same dosage in normal (n=5) and TIVCC (n=6) dogs. Intracoronary infusion of ET-1 significantly decreased coronary blood flow and increased coronary vascular resistance in normal dogs; this effect was significantly attenuated in TIVCC compared with normal dogs. The percent changes in coronary blood flow and coronary vascular resistance in the TIVCC compared with the normal dogs was -11±8% versus -48±7% (P<.01) and 29±10% versus 105±23% (P<.01), respectively. There was no significant effect on coronary blood flow, coronary vascular resistance, or coronary artery diameter in normal dogs that received an intracoronary infusion of sarafotoxin. In contrast, the administration of intracoronary sarafotoxin in TIVCC compared with normal dogs resulted in significant percent changes in coronary blood flow and coronary vascular resistance (-31±4% versus -7±3% [P<.001] and 53±12% versus 12±8% [P<.02], respectively).
Conclusions The present study demonstrates an attenuated coronary vasoconstrictor response to ET-1 with an enhanced vasoconstrictor response to sarafotoxin and suggests an alteration in coronary ET receptor sensitivity in experimental heart failure.
Key Words: endothelin • receptors • arteries • heart failure • vasoconstriction
This article has been cited by other articles:
 |
|
 |
|
  A. Wackenfors, R. Ingemansson, and M. Malmsjo Endothelin receptors in endothelium-denuded human coronary artery bypass grafts and coronary arteries Ann. Thorac. Surg., March 1, 2003; 75(3): 874 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-S. Ding, C. Qiu, P. Hess, J.-F. Xi, J.-P. Clozel, and M. Clozel Chronic endothelin receptor blockade prevents renal vasoconstriction and sodium retention in rats with chronic heart failure Cardiovasc Res, March 1, 2002; 53(4): 963 - 970. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-M. Herrmann, K. Schmidt-Petersen, J. Pfeifer, A. Perrot, N. Bit-Avragim, C. Eichhorn, R. Dietz, R. Kreutz, M. Paul, and K.J. Osterziel A polymorphism in the endothelin-A receptor gene predicts survival in patients with idiopathic dilated cardiomyopathy Eur. Heart J., October 2, 2001; 22(20): 1948 - 1953. [Abstract] [PDF]
|
|
|
|
 |
|
 M. C. Petrie, C. Hillier, F. Johnston, and J. J.V. McMurray Effect of Neutral Endopeptidase Inhibition on the Actions of Adrenomedullin and Endothelin-1 in Resistance Arteries From Patients With Chronic Heart Failure Hypertension, September 1, 2001; 38(3): 412 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. L. David, M. H. C. Carvalho, A. L.N. Cobra, D. Nigro, Z. B. Fortes, N. A. Reboucas, and R. C.A. Tostes Ovarian Hormones Modulate Endothelin-1 Vascular Reactivity and mRNA Expression in DOCA-Salt Hypertensive Rats Hypertension, September 1, 2001; 38(3): 692 - 696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bergdahl, S. Valdemarsson, M. Adner, X.-Y. Sun, T. Hedner, and L. Edvinsson Enhanced endothelin-1-induced contractions in mesenteric arteries from rats with congestive heart failure: role of ETB receptors Eur J Heart Fail, June 1, 2001; 3(3): 293 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Torre-Amione, J. B. Young, J.-B. Durand, B. Bozkurt, D. L. Mann, I. Kobrin, and C. M. Pratt Hemodynamic Effects of Tezosentan, an Intravenous Dual Endothelin Receptor Antagonist, in Patients With Class III to IV Congestive Heart Failure Circulation, February 20, 2001; 103(7): 973 - 980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Elijovich, C. L. Laffer, E. Amador, H. Gavras, M. R. Bresnahan, and E. L. Schiffrin Regulation of Plasma Endothelin by Salt in Salt-Sensitive Hypertension Circulation, January 16, 2001; 103(2): 263 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Thorin, M. Lucas, P. Cernacek, and J. Dupuis Role of ETA receptors in the regulation of vascular reactivity in rats with congestive heart failure Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H844 - H851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P Love, C. J Ferro, W. G Haynes, C. Plumpton, A. P Davenport, D. J Webb, and J. J.V McMurray Endothelin receptor antagonism in patients with chronic heart failure Cardiovasc Res, July 1, 2000; 47(1): 166 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. M. Best, L. O. Lerman, J. C. Romero, D. Richardson, D. R. Holmes Jr, and A. Lerman Coronary Endothelial Function Is Preserved With Chronic Endothelin Receptor Antagonism in Experimental Hypercholesterolemia In Vitro Arterioscler Thromb Vasc Biol, November 1, 1999; 19(11): 2769 - 2775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. M. Best, C. J. McKenna, D. Hasdai, D. R. Holmes Jr, and A. Lerman Chronic Endothelin Receptor Antagonism Preserves Coronary Endothelial Function in Experimental Hypercholesterolemia Circulation, April 6, 1999; 99(13): 1747 - 1752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Cowburn, J. G. F. Cleland, J. D. McArthur, M. R. MacLean, J. J. V. McMurray, H. J. Dargie, and J. J. Morton EndothelinB receptors are functionally important in mediating vasoconstriction in the systemic circulation in patients with left ventricular systolic dysfunction J. Am. Coll. Cardiol., March 15, 1999; 33(4): 932 - 938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Mundhenke, B Schwartzkopff, M Köstering, U Deska, R M Klein, and B E Strauer Endogenous plasma endothelin concentrations and coronary circulation in patients with mild dilated cardiomyopathy Heart, March 1, 1999; 81(3): 278 - 284. [Abstract] [Full Text]
|
|
|
|
|
|
F. G. Spinale, R. Mukherjee, R. S. Krombach, M. J. Clair, J. W. Hendrick, W. V. Houck, L. Hebbar, S. B. Kribbs, J. L. Zellner, and M. G. Dodd Chronic Amlodipine Treatment During the Development of Heart Failure Circulation, October 20, 1998; 98(16): 1666 - 1674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Bankers-Fulbright, G. M. Kephart, D. A. Loegering, A. L. Bradford, S. Okada, H. Kita, and G. J. Gleich Sulfonylureas Inhibit Cytokine-Induced Eosinophil Survival and Activation J. Immunol., June 1, 1998; 160(11): 5546 - 5553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.S. Krombach, M. J Clair, J. W Hendrick, W. V Houck, J. L Zellner, S. B Kribbs, S. Whitebread, R. Mukherjee, M. de Gasparo, and F. G Spinale Angiotensin converting enzyme inhibition, AT1 receptor inhibition, and combination therapy with pacing induced heart failure: effects on left ventricular performance and regional blood flow patterns Cardiovasc Res, June 1, 1998; 38(3): 631 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Verhaar, F. E. Strachan, D. E. Newby, N. L. Cruden, H. A. Koomans, T. J. Rabelink, and D. J. Webb Endothelin-A Receptor Antagonist–Mediated Vasodilatation Is Attenuated by Inhibition of Nitric Oxide Synthesis and by Endothelin-B Receptor Blockade Circulation, March 3, 1998; 97(8): 752 - 756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hasdai, P. J.M. Best, C. R. Cannan, V. Mathew, R. S. Schwartz, D. R. Holmes Jr, and A. Lerman Acute Endothelin-Receptor Inhibition Does Not Attenuate Acetylcholine-Induced Coronary Vasoconstriction in Experimental Hypercholesterolemia Arterioscler Thromb Vasc Biol, January 1, 1998; 18(1): 108 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Rasmussen, M. Jougasaki, T. Supaporn, J. W. Hallett Jr., D. P. Brooks, and J. C. Burnett Jr. Cardiovascular actions of ET-B activation in vivo and modulation by receptor antagonism Am J Physiol Regulatory Integrative Comp Physiol, January 1, 1998; 274(1): R131 - R138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Adner, E. Uddman, L. O. Cardell, and L. Edvinsson Regional variation in appearance of vascular contractile endothelin-B receptors following organ culture Cardiovasc Res, January 1, 1998; 37(1): 254 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hasdai, V. Mathew, R. S. Schwartz, L. A. Smith, D. R. Holmes Jr, Z. S. Katusic, and A. Lerman Enhanced Endothelin-B-Receptor–Mediated Vasoconstriction of Small Porcine Coronary Arteries in Diet-Induced Hypercholesterolemia Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2737 - 2743. [Abstract] [Full Text]
|
|
|
|
|
|
P. Mulder, V. Richard, G. Derumeaux, M. Hogie, J. P. Henry, F. Lallemand, P. Compagnon, B. Mace, E. Comoy, B. Letac, et al. Role of Endogenous Endothelin in Chronic Heart Failure : Effect of Long-term Treatment With an Endothelin Antagonist on Survival, Hemodynamics, and Cardiac Remodeling Circulation, September 16, 1997; 96(6): 1976 - 1982. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Yazaki and T. Yamazaki Reversing Congestive Heart Failure With Endothelin Receptor Antagonists Circulation, April 1, 1997; 95(7): 1752 - 1754. [Full Text]
|
|
|
|
|
|
F. G. Spinale, J. D. Walker, R. Mukherjee, J. P. Iannini, A. T. Keever, and K. P. Gallagher Concomitant Endothelin Receptor Subtype-A Blockade During the Progression of Pacing-Induced Congestive Heart Failure in Rabbits : Beneficial Effects on Left Ventricular and Myocyte Function Circulation, April 1, 1997; 95(7): 1918 - 1929. [Abstract] [Full Text]
|
|
|
|
|
|
M. P. Love, W. G. Haynes, G. A. Gray, D. J. Webb, and J. J.V. McMurray Vasodilator Effects of Endothelin-Converting Enzyme Inhibition and Endothelin ETA Receptor Blockade in Chronic Heart Failure Patients Treated With ACE Inhibitors Circulation, November 1, 1996; 94(9): 2131 - 2137. [Abstract] [Full Text]
|
|