(Circulation. 1996;94:2131-2137.)
© 1996 American Heart Association, Inc.
Articles |
Vasodilator Effects of Endothelin-Converting Enzyme Inhibition and Endothelin ETA Receptor Blockade in Chronic Heart Failure Patients Treated With ACE Inhibitors
the Medical Research Council Clinical Research Initiative in Heart Failure, University of Glasgow (M.P.L., J.J.V.M.), and the University of Edinburgh Department of Medicine, Western General Hospital (W.G.H., G.A.G., D.J.W.), Scotland, UK.
Background The importance of endothelin-1 in chronic heart failure (CHF) is unclear. We therefore investigated the effects of endothelin-converting enzyme (ECE) inhibition and endothelin ETA receptor blockade in CHF patients treated with ACE inhibitors. We also compared the function of ETA and ETB receptors in healthy subjects and patients with CHF.
Methods and Results Locally active doses of study drugs were infused into the nondominant brachial artery while forearm blood flow (FBF) was measured by venous occlusion plethysmography. In CHF patients (n=10), phosphoramidon (a combined ECE and neutral endopeptidase inhibitor) and BQ-123 (an ETA receptor antagonist) increased FBF by 52±10% (P=.0006) and 31±6% (P=.002), respectively, and thiorphan (a selective neutral endopeptidase inhibitor) reduced FBF by 15±5% (P=.0007). Forearm vasoconstriction to endothelin-1 (an ETA and ETB receptor agonist) was significantly blunted in CHF patients compared with control subjects (both n=10; CHF versus control subjects, P<.001), whereas vasoconstriction to sarafotoxin S6c (an ETB receptor agonist) was significantly enhanced in CHF patients compared with control subjects (both n=10; CHF versus control subjects, P<.05).
Conclusions ECE inhibitors and ETA receptor antagonists may be useful as vasodilator agents in CHF patients already receiving treatment with an ACE inhibitor. Both ETA and ETB receptors can mediate agonist-induced vasoconstriction in healthy subjects and patients with CHF, but further studies are required to clarify the contribution of each receptor subtype in mediating the effects of endogenous endothelin-1.
Key Words: endothelin • heart failure • vasodilatation • vasoconstriction • receptors
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|
|
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|
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|
|
|
|
|
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|
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|
|
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|
|
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|
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|
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|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
P. Mulder, V. Richard, F. Bouchart, G. Derumeaux, K. Munter, and C. Thuillez Selective ETA receptor blockade prevents left ventricular remodeling and deterioration of cardiac function in experimental heart failure Cardiovasc Res, September 1, 1998; 39(3): 600 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. G. Haynes, C. J. Ferro, D. J. Webb, B. K. Kramer, F. Schweda, G. A.J. Riegger, H. Krum, Y. Lacourciere, and V. Charlon Bosentan in Essential Hypertension N. Engl. J. Med., July 30, 1998; 339(5): 346 - 347. [Full Text]
|
|
|
|
|
|
C. J. Ferro, J. C. Spratt, W. G. Haynes, and D. J. Webb Inhibition of Neutral Endopeptidase Causes Vasoconstriction of Human Resistance Vessels In Vivo Circulation, June 16, 1998; 97(23): 2323 - 2330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ergul, K. Shoemaker, D. Puett, and R. L. Tackett Gender Differences in the Expression of Endothelin Receptors in Human Saphenous Veins In Vitro J. Pharmacol. Exp. Ther., May 1, 1998; 285(2): 511 - 517. [Abstract] [Full Text]
|
|
|
|
|
|
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|
|
|
|
|
|
D. D. Borgeson, J. A. Grantham, E. E. Williamson, A. Luchner, M. M. Redfield, T. J. Opgenorth, and J. C. Burnett Jr Chronic Oral Endothelin Type A Receptor Antagonism in Experimental Heart Failure Hypertension, March 1, 1998; 31(3): 766 - 770. [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]
|
|
|
|
 |
|
 D. E Newby and D. J Webb The endothelin system in cardiovascular disease BMJ, February 22, 1997; 314(7080): 531 - 531. [Full Text]
|
|
|
|
 |
|
 J. P.J. Halcox, K. R.A. Nour, G. Zalos, and A. A. Quyyumi Coronary Vasodilation and Improvement in Endothelial Dysfunction With Endothelin ETA Receptor Blockade Circ. Res., November 23, 2001; 89(11): 969 - 976. [Abstract] [Full Text] [PDF]
|
|