Circulation, Vol 89, 1203-1208, Copyright © 1994 by American Heart Association
B Seo, BS Oemar, R Siebenmann, L von Segesser and TF Luscher
BACKGROUND: Endothelin (ET)-1 has potent vascular effects. Two endothelin
receptors have been cloned, namely, the ETA receptor, which preferentially
binds ET-1, and the ETB receptor, which equally binds ET- 1 and ET-3 and
preferentially sarafotoxin S6c. We characterized endothelin receptor
subtypes on vascular smooth muscle and endothelium of isolated human
internal mammary artery (IMA) and vein (IMV) and porcine coronary artery
(PCA) using the ETA antagonists FR139317 and BQ- 123, the ETB ligand
sarafotoxin S6c, and the ETA/ETB antagonist Ro 47- 0203 (bosentan). METHODS
AND RESULTS: In endothelium-denuded IMA and PCA and less so in IMV,
FR139317 and BQ-123 (in PCA only) shifted the concentration-contraction
curves to ET-1 parallel to the right. However, even at 10(-5) mol/L,
FR139317 did not inhibit a high- sensitivity portion of the
concentration-contraction curve. Moreover, the ETB receptor agonist
sarafotoxin S6c induced contraction in vessels preincubated with FR139317.
IMV was significantly more sensitive to the contractile effect of ET-1 and
sarafotoxin S6c than was IMA (P < .05). Prolonged incubation with
sarafotoxin S6c (to downregulate ETB receptors) and FR139317 eliminated the
contraction resistant to FR139317. The ETA/ETB receptor antagonist bosentan
caused a parallel shift of the concentration-contraction curve to the right
at all concentrations of endothelin. ETB receptor mRNA was detected by
Northern blot analysis in IMA and aortic smooth muscle cells. In
precontracted IMA and PCA with endothelium, sarafotoxin S6c did not cause
endothelium-dependent relaxations, whereas transient responses occurred in
IMV. CONCLUSIONS: Vascular smooth muscle cells of human IMA, IMV, and PCA
contain both ETA and ETB receptors, whereas the endothelium of IMA and PCA
does not express functional ETB receptors linked to nitric oxide and/or
prostacyclin production. Hence, inhibition of endothelin-induced
contraction in patients requires the use of combined ETA/ETB antagonists.
ARTICLES
Both ETA and ETB receptors mediate contraction to endothelin-1 in human blood vessels
Department of Research, University Hospitals, Basel, Switzerland.
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G. W Moe, A. Albernaz, G. O Naik, M. Kirchengast, and D. J Stewart Beneficial effects of long-term selective endothelin type A receptor blockade in canine experimental heart failure Cardiovasc Res, September 1, 1998; 39(3): 571 - 579. [Abstract] [Full Text] [PDF]
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R. Choussat, L. Hittinger, F. Barbe, G. Maistre, A. Carayon, B. Crozatier, and J. Su Acute effects of an endothelin-1 receptor antagonist bosentan at different stages of heart failure in conscious dogs Cardiovasc Res, September 1, 1998; 39(3): 580 - 588. [Abstract] [Full Text] [PDF]
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D. Hasdai, D. R. Holmes Jr., D. M. Richardson, U. Izhar, and A. Lerman Insulin and IGF-I attenuate the coronary vasoconstrictor effects of endothelin-1 but not of sarafotoxin 6c Cardiovasc Res, September 1, 1998; 39(3): 644 - 650. [Abstract] [Full Text] [PDF]
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Y. Zhang, J. R. Oliver, and J. D. Horowitz Endothelin B receptor-mediated vasoconstriction induced by endothelin A receptor antagonist Cardiovasc Res, September 1, 1998; 39(3): 665 - 673. [Abstract] [Full Text] [PDF]
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G. Szabo, L. Fazekas, S. Bahrle, D. MacDonald, N. Stumpf, C. F Vahl, and S. Hagl Endothelin-A and -B antagonists protect myocardial and endothelial function after ischemia/reperfusion in a rat heart transplantation model Cardiovasc Res, September 1, 1998; 39(3): 683 - 690. [Abstract] [Full Text] [PDF]
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 A. Iannaccone, C. Letizia, S. Pazzaglia, E. M Vingolo, G. Clemente, and M. R Pannarale Plasma endothelin-1 concentrations in patients with retinal vein occlusions Br J Ophthalmol, May 1, 1998; 82(5): 498 - 503. [Abstract] [Full Text]
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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]
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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]
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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]
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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]
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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]
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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]
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D. Eguchi, J. Nishimura, S. Kobayashi, K. Komori, K. Sugimachi, and H. Kanaide Down-regulation of endothelin B receptors in autogenous saphenous veins grafted into the arterial circulation Cardiovasc Res, August 1, 1997; 35(2): 360 - 367. [Abstract] [Full Text] [PDF]
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J. G. Filep Endogenous Endothelin Modulates Blood Pressure, Plasma Volume, and Albumin Escape After Systemic Nitric Oxide Blockade Hypertension, July 1, 1997; 30(1): 22 - 28. [Abstract] [Full Text]
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R. Lundblad, O. Moen, and E. Fosse Endothelin-1 and Neutrophil Activation During Heparin-Coated Cardiopulmonary Bypass Ann. Thorac. Surg., May 1, 1997; 63(5): 1361 - 1367. [Abstract] [Full Text]
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Y. Yazaki and T. Yamazaki Reversing Congestive Heart Failure With Endothelin Receptor Antagonists Circulation, April 1, 1997; 95(7): 1752 - 1754. [Full Text]
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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]
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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]
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 P. Holm, J. Liska, M. Clozel, and A. Franco-Cereceda THE ENDOTHELIN ANTAGONIST BOSENTAN: HEMODYNAMIC EFFECTS DURING NORMOXIA AND HYPOXIC PULMONARY HYPERTENSION IN PIGS J. Thorac. Cardiovasc. Surg., October 1, 1996; 112(4): 890 - 897. [Abstract] [Full Text]
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J. Angulo, C. F. Sanchez-Ferrer, C. Peiro, J. Marin, and L. Rodriguez-Manas Impairment of Endothelium-Dependent Relaxation by Increasing Percentages of Glycosylated Human Hemoglobin: Possible Mechanisms Involved Hypertension, October 1, 1996; 28(4): 583 - 592. [Abstract] [Full Text]
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H. Shimoyama, H. N. Sabbah, S. Borzak, M. Tanimura, S. Shevlyagin, G. Scicli, and S. Goldstein Short-term Hemodynamic Effects of Endothelin Receptor Blockade in Dogs With Chronic Heart Failure Circulation, August 15, 1996; 94(4): 779 - 784. [Abstract] [Full Text]
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P. Holm and A. Franco-Cereceda TISSUE CONCENTRATIONS OF ENDOTHELINS AND FUNCTIONAL EFFECTS OF ENDOTHELIN-RECEPTOR ACTIVATION IN HUMAN ARTERIES AND VEINS J. Thorac. Cardiovasc. Surg., August 1, 1996; 112(2): 264 - 272. [Abstract] [Full Text]
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R. R. Wenzel, N. Duthiers, G. Noll, J. Bucher, U. Kaufmann, and T. F. Luscher Endothelin and Calcium Antagonists in the Skin Microcirculation of Patients With Coronary Artery Disease Circulation, August 1, 1996; 94(3): 316 - 322. [Abstract] [Full Text]
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W. G. Haynes, C. J. Ferro, K. P. J. O'Kane, D. Somerville, C. C. Lomax, and D. J. Webb Systemic Endothelin Receptor Blockade Decreases Peripheral Vascular Resistance and Blood Pressure in Humans Circulation, May 15, 1996; 93(10): 1860 - 1870. [Abstract] [Full Text]
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Y. Takeda, I. Miyamori, P. Wu, T. Yoneda, K. Furukawa, and R. Takeda Effects of an Endothelin Receptor Antagonist in Rats With Cyclosporine-Induced Hypertension Hypertension, December 1, 1995; 26(6): 932 - 936. [Abstract] [Full Text]
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C. R. Cannan, J. C. Burnett Jr, R. R. Brandt, and A. Lerman Endothelin at Pathophysiological Concentrations Mediates Coronary Vasoconstriction via the Endothelin-A Receptor Circulation, December 1, 1995; 92(11): 3312 - 3317. [Abstract] [Full Text]
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R. M. Touyz, L. Y. Deng, and E. L. Schiffrin Endothelin Subtype B Receptor–Mediated Calcium and Contractile Responses in Small Arteries of Hypertensive Rats Hypertension, December 1, 1995; 26(6): 1041 - 1045. [Abstract] [Full Text]
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 E. R. Levin Endothelins N. Engl. J. Med., August 10, 1995; 333(6): 356 - 363. [Full Text] [PDF]
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W. G. Haynes, F. E. Strachan, and D. J. Webb Endothelin ETA and ETB Receptors Cause Vasoconstriction of Human Resistance and Capacitance Vessels In Vivo Circulation, August 1, 1995; 92(3): 357 - 363. [Abstract] [Full Text]
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E. L. Schiffrin Endothelin: Potential Role in Hypertension and Vascular Hypertrophy Hypertension, June 1, 1995; 25(6): 1135 - 1143. [Abstract] [Full Text]
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