Circulation, Vol 83, 1808-1814, Copyright © 1991 by American Heart Association
A Lerman, FL Hildebrand Jr, LL Aarhus and JC Burnett Jr
BACKGROUND. Endothelin is an endothelium-derived peptide that produces
sustained contraction of arterial and venous smooth muscle in vitro.
Several studies have established endothelin as a systemic, renal, and
coronary vasoconstrictor in vivo at pharmacological concentrations. Such
concentrations of endothelin were antinatriuretic in association with
activation of the renin-angiotensin-aldosterone system. Recent studies have
demonstrated that endothelin is present in the plasma and that its plasma
concentrations are increased in various pathological states associated with
systemic and renal vasoconstriction. To date, it remains unclear if such
increases in circulating endothelin are associated with biological
activity. Thus, the objective of this study was to determine the biological
action of endothelin on cardiorenal and endocrine function through
administration of exogenous endothelin, which achieves plasma
concentrations that have been reported in various pathophysiological
conditions. METHODS AND RESULTS. Experiments were conducted in two groups
of anesthetized dogs. In group 1, endothelin-1 was infused intravenously at
2.5 ng/kg/ml (n = 6), which produced a doubling of circulating
concentrations. Group 2 (n = 8) received saline vehicle to serve as a time
control. The current studies demonstrate that a twofold increase in plasma
endothelin concentrations did not affect mean blood pressure or coronary
blood flow. Heart rate and cardiac output decreased in association with
increased renal and systemic vascular resistances and antinatriuresis.
CONCLUSIONS. The present studies demonstrate that endothelin at
pathophysiological plasma concentrations produced by exogenous endothelin
has biological action. These studies support a functional role for
endogenous endothelin as a potentially pathophysiological vasoconstrictor
peptide hormone in the regulation of cardiovascular, renal, and endocrine
function.
ARTICLES
Endothelin has biological actions at pathophysiological concentrations
Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, MN 55905.
This article has been cited by other articles:
 |
|
 |
|
  J. R. Alegria, J. Herrmann, D. R. Holmes Jr, A. Lerman, and C. S. Rihal Myocardial bridging Eur. Heart J., June 2, 2005; 26(12): 1159 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Parker and J. J. Thiessen Increased endothelin-1 production in patients with chronic heart failure Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H1141 - H1145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Schirger, H. H. Chen, M. Jougasaki, O. Lisy, G. Boerrigter, A. Cataliotti, and J. C. Burnett Jr Endothelin A Receptor Antagonism in Experimental Congestive Heart Failure Results in Augmentation of the Renin-Angiotensin System and Sustained Sodium Retention Circulation, January 20, 2004; 109(2): 249 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gattenlohner, C. Waller, G. Ertl, B.-D. Bultmann, H.-K. Muller-Hermelink, and A. Marx NCAM(CD56) and RUNX1(AML1) Are Up-Regulated in Human Ischemic Cardiomyopathy and a Rat Model of Chronic Cardiac Ischemia Am. J. Pathol., September 1, 2003; 163(3): 1081 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Maeda, T. Tanabe, T. Miyauchi, T. Otsuki, J. Sugawara, M. Iemitsu, S. Kuno, R. Ajisaka, I. Yamaguchi, and M. Matsuda Aerobic exercise training reduces plasma endothelin-1 concentration in older women J Appl Physiol, July 1, 2003; 95(1): 336 - 341. [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]
|
|
|
|
 |
|
 A. Luchner, M. Jougasaki, E. Friedrich, D. D. Borgeson, T. L. Stevens, M. M. Redfield, G. A. J. Riegger, and J. C. Burnett Jr. Activation of cardiorenal and pulmonary tissue endothelin-1 in experimental heart failure Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2000; 279(3): R974 - R979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Zolk and M. Bohm The role of the cardiac endothelin system in heart failure Nephrol. Dial. Transplant., June 1, 2000; 15(6): 758 - 760. [Full Text] [PDF]
|
|
|
|
|
|
H. Kjekshus, O. A. Smiseth, R. Klinge, E. Oie, M. E. Hystad, and H. Attramadal Regulation of ET: pulmonary release of ET contributes to increased plasma ET levels and vasoconstriction in CHF Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1299 - H1310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wei and J. C. Burnett Jr. Inhibition by calcium antagonism of circulating and renal endothelin in experimental congestive heart failure Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H263 - H268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Battistelli, M. Billi, G. Manasse, A. Vittoria, F. Roviello, and S. Forconi Behavior of Circulating Endothelin-1 in a Group of Patients with Acute Myocardial Infarction Angiology, August 1, 1999; 50(8): 629 - 638. [Abstract] [PDF]
|
|
|
|
|
|
C. Sartori, L. Vollenweider, B.-M. Loffler, A. Delabays, P. Nicod, P. Bartsch, and U. Scherrer Exaggerated Endothelin Release in High-Altitude Pulmonary Edema Circulation, May 25, 1999; 99(20): 2665 - 2668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Parker, J. J. Thiessen, R. Reilly, J. H. Tong, D. J. Stewart, and A. S. Pandey Human Endothelin-1 Clearance Kinetics Revealed by a Radiotracer Technique J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 261 - 265. [Abstract] [Full Text]
|
|
|
|
|
|
K. Onishi, M. Ohno, W. C. Little, and C.-P. Cheng Endogenous Endothelin-1 Depresses Left Ventricular Systolic and Diastolic Performance in Congestive Heart Failure J. Pharmacol. Exp. Ther., March 1, 1999; 288(3): 1214 - 1222. [Abstract] [Full Text]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 T. Tsutamoto, A. Wada, T. Hisanaga, K. Maeda, M. Ohnishi, N. Mabuchi, M. Sawaki, M. Hayashi, M. Fujii, and M. Kinoshita Relationship between endothelin-1 extraction in the peripheral circulation and systemic vascular resistance in patients with severe congestive heart failure J. Am. Coll. Cardiol., February 1, 1999; 33(2): 530 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dupuis, J.-L. Rouleau, and P. Cernacek Reduced Pulmonary Clearance of Endothelin-1 Contributes to the Increase of Circulating Levels in Heart Failure Secondary to Myocardial Infarction Circulation, October 20, 1998; 98(16): 1684 - 1687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Geny, F. Piquard, J. Lonsdorfer, and P. Haberey Endothelin and heart transplantation Cardiovasc Res, September 1, 1998; 39(3): 556 - 562. [Full Text] [PDF]
|
|
|
|
|
|
B. Bozkurt, S. B. Kribbs, F. J. Clubb Jr, L. H. Michael, V. V. Didenko, P. J. Hornsby, Y. Seta, H. Oral, F. G. Spinale, and D. L. Mann Pathophysiologically Relevant Concentrations of Tumor Necrosis Factor-{alpha} Promote Progressive Left Ventricular Dysfunction and Remodeling in Rats Circulation, April 14, 1998; 97(14): 1382 - 1391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Thorin, P. Cernacek, and J. Dupuis Endothelin-1 Regulates Tone of Isolated Small Arteries in the Rat : Effect of Hyperendothelinemia Hypertension, April 1, 1998; 31(4): 1035 - 1041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 C. Haug, W. Koenig, M. Hoeher, M. Kochs, V. Hombach, A. Gruenert, and H. Osterhues Direct enzyme immunometric measurement of plasma big endothelin-1 concentrations and correlation with indicators of left ventricular function Clin. Chem., February 1, 1998; 44(2): 239 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Thorin, T.-D. Nguyen, A. Bouthillier, and F. M. Faraci Control of Vascular Tone by Endogenous Endothelin-1 in Human Pial Arteries • Editorial Comment Stroke, January 1, 1998; 29(1): 175 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Disashi, H. Nonoguchi, T. Iwaoka, S. Naomi, Y. Nakayama, K. Shimada, K. Tanzawa, and K. Tomita Endothelin Converting Enzyme-1 Gene Expression in the Kidney of Spontaneously Hypertensive Rats Hypertension, December 1, 1997; 30(6): 1591 - 1597. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Kapiotis, B. Jilma, T. Szalay, E. Dirnberger, O. Wagner, H.-G. Eichler, and W. Speiser Evidence Against an Effect of Endothelin-1 on Blood Coagulation, Fibrinolysis, and Endothelial Cell Integrity in Healthy Men Arterioscler. Thromb. Vasc. Biol., November 1, 1997; 17(11): 2861 - 2867. [Abstract] [Full Text]
|
|
|
|
|
|
J.-P. Gratton, G. Cournoyer, B.-M. Loffler, P. Sirois, and P. D'Orleans-Juste ETB Receptor and Nitric Oxide Synthase Blockade Induce BQ-123–Sensitive Pressor Effects in the Rabbit Hypertension, November 1, 1997; 30(5): 1204 - 1209. [Abstract] [Full Text]
|
|
|
|
|
|
R. R. Brandt, M. T. Mattingly, A. L. Clavell, P. L. Barclay, and J. C. Burnett Jr Neutral Endopeptidase Regulates C-Type Natriuretic Peptide Metabolism But Does Not Potentiate Its Bioactivity In Vivo Hypertension, August 1, 1997; 30(2): 184 - 190. [Abstract] [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]
|
|
|
|
|
|
P. Cacoub, R. Dorent, P. Nataf, A. Carayon, M. Riquet, E. Noe, J. C. Piette, P. Godeau, and I. Gandjbakhch Endothelin-1 in the lungs of patients with pulmonary hypertension Cardiovasc Res, January 1, 1997; 33(1): 196 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dupuis, D. J. Stewart, P. Cernacek, and G. Gosselin Human Pulmonary Circulation Is an Important Site for Both Clearance and Production of Endothelin-1 Circulation, October 1, 1996; 94(7): 1578 - 1584. [Abstract] [Full Text]
|
|
|
|
|
|
T. S. Rector, A. J. Bank, K. A. Mullen, L. K. Tschumperlin, R. Sih, K. Pillai, and S. H. Kubo Randomized, Double-Blind, Placebo-Controlled Study of Supplemental Oral L-Arginine in Patients With Heart Failure Circulation, June 15, 1996; 93(12): 2135 - 2141. [Abstract] [Full Text]
|
|
|
|
|
|
C. R. Cannan, J. C. Burnett Jr, and A. Lerman Enhanced Coronary Vasoconstriction to Endothelin-BReceptor Activation in Experimental Congestive Heart Failure Circulation, February 15, 1996; 93(4): 646 - 651. [Abstract] [Full Text]
|
|
|
|
|
|
K. Hasegawa, H. Fujiwara, M. Koshiji, T. Inada, S. Ohtani, K. Doyama, M. Tanaka, A. Matsumori, T. Fujiwara, G. Shirakami, et al. Endothelin-1 and Its Receptor in Hypertrophic Cardiomyopathy Hypertension, February 1, 1996; 27(2): 259 - 264. [Abstract] [Full Text]
|
|
|
|
|
|
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]
|
|
|
|
|
|
A. Lerman, D. R. Holmes Jr, M. R. Bell, K. N. Garratt, R. A. Nishimura, and J. C. Burnett Jr Endothelin in Coronary Endothelial Dysfunction and Early Atherosclerosis in Humans Circulation, November 1, 1995; 92(9): 2426 - 2431. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. R. Levin Endothelins N. Engl. J. Med., August 10, 1995; 333(6): 356 - 363. [Full Text] [PDF]
|
|