| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 1999;33:753-758.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Role of Endothelin in the Increased Vascular Tone of Patients With Essential Hypertension
From the Cardiology Branch (C.C., C.M.K., R.O.C., J.A.P.) and the Division of Epidemiology and Clinical Applications (M.W.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
Correspondence to Dr Julio A. Panza, Cardiology Branch, NHLBI, NIH, Building 10, Room 7B-15, Bethesda, MD 20892-1650. E-mail panzaj{at}gwgate.nhlbi.nih.gov
Abstract—We investigated the possible role of endothelin in the increased vasoconstrictor tone of hypertensive patients using antagonists of endothelin receptors. Forearm blood flow (FBF) responses (strain-gauge plethysmography) to intraarterial infusion of blockers of endothelin-A (ETA) (BQ-123) and endothelin-B (ETB) (BQ-788) receptors, separately and in combination, were measured in hypertensive patients and normotensive control subjects. In healthy subjects, BQ-123 alone or in combination with BQ-788 did not significantly modify FBF (P=0.78 and P=0.63, respectively). In hypertensive patients, in contrast, BQ-123 increased FBF by 33±7% (P<0.001 versus baseline), and the combination of BQ-123 and BQ-788 resulted in a greater vasodilator response (63±12%; P=0.006 versus BQ-123 alone in the same subjects). BQ-788 produced a divergent vasoactive effect in the two groups, with a decrease of FBF (17±5%; P=0.004 versus baseline) in control subjects and transient vasodilation (15±7% after 20 minutes) in hypertensive patients (P<0.001, hypertensives versus controls). The vasoconstrictor response to endothelin-1 was slightly higher (P=0.04) in hypertensive patients (46±4%) than in control subjects (32±4%). Our data indicate that patients with essential hypertension have increased vascular endothelin activity, which may be of pathophysiological relevance to their increased vascular tone. In these patients, nonselective ETA and ETB blockade seems to produce a greater vasodilator effect than selective ETA blockade.
Key Words: endothelin • hypertension, essential • vascular tone • receptors, endothelin • blood flow
This article has been cited by other articles:
 |
|
 |
|
  M. Tesauro, F. Schinzari, V. Rovella, N. Di Daniele, D. Lauro, N. Mores, A. Veneziani, and C. Cardillo Ghrelin Restores the Endothelin 1/Nitric Oxide Balance in Patients With Obesity-Related Metabolic Syndrome Hypertension, November 1, 2009; 54(5): 995 - 1000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Larose, D. Behrendt, S. Kinlay, A. P. Selwyn, P. Ganz, and J. C. Fang Endothelin-1 Is a Key Mediator of Coronary Vasoconstriction in Patients With Transplant Coronary Arteriosclerosis Circ Heart Fail, September 1, 2009; 2(5): 409 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. E. Kandalaft, A. Facciabene, R. J. Buckanovich, and G. Coukos Endothelin B Receptor, a New Target in Cancer Immune Therapy Clin. Cancer Res., July 15, 2009; 15(14): 4521 - 4528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Iglarz, C. Binkert, K. Morrison, W. Fischli, J. Gatfield, A. Treiber, T. Weller, M. H. Bolli, C. Boss, S. Buchmann, et al. Pharmacology of Macitentan, an Orally Active Tissue-Targeting Dual Endothelin Receptor Antagonist J. Pharmacol. Exp. Ther., December 1, 2008; 327(3): 736 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Dhaun, J. Goddard, D. E. Kohan, D. M. Pollock, E. L. Schiffrin, and D. J. Webb Role of Endothelin-1 in Clinical Hypertension: 20 Years On Hypertension, September 1, 2008; 52(3): 452 - 459. [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Gomez, M. J. Moreno, R. M. Baldrich, and A. Hernandez Endothelin-1 Molecular Ribonucleic Acid Expression in Pulmonary Hypertensive and Nonhypertensive Chickens Poult. Sci., July 1, 2008; 87(7): 1395 - 1401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Bohm and J. Pernow The importance of endothelin-1 for vascular dysfunction in cardiovascular disease Cardiovasc Res, October 1, 2007; 76(1): 8 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Van Guilder, C. M. Westby, J. J. Greiner, B. L. Stauffer, and C. A. DeSouza Endothelin-1 Vasoconstrictor Tone Increases With Age in Healthy Men But Can Be Reduced by Regular Aerobic Exercise Hypertension, August 1, 2007; 50(2): 403 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Xu, G. D. Fink, and J. J. Galligan Increased sympathetic venoconstriction and reactivity to norepinephrine in mesenteric veins in anesthetized DOCA-salt hypertensive rats Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H160 - H168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bussemaker, F. Pistrosch, S. Forster, K. Herbrig, P. Gross, J. Passauer, and R. P. Brandes Rho kinase contributes to basal vascular tone in humans: role of endothelium-derived nitric oxide Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H541 - H547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Gomez, M. J. Moreno, A. Iglesias, P. X. Coral, and A. Hernandez Endothelin 1, its Endothelin Type A Receptor, Connective Tissue Growth Factor, Platelet-Derived Growth Factor, and Adrenomedullin Expression in Lungs of Pulmonary Hypertensive and Nonhypertensive Chickens Poult. Sci., May 1, 2007; 86(5): 909 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P.J. Halcox, K. R.A. Nour, G. Zalos, and A. A. Quyyumi Endogenous Endothelin in Human Coronary Vascular Function: Differential Contribution of Endothelin Receptor Types A and B Hypertension, May 1, 2007; 49(5): 1134 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Barac, U. Campia, and J. A. Panza Methods for Evaluating Endothelial Function in Humans Hypertension, April 1, 2007; 49(4): 748 - 760. [Full Text] [PDF]
|
|
|
|
|
|
M. Feletou and P. M. Vanhoutte Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture) Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H985 - H1002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Tirapelli, D. A. Casolari, A. C. Montezano, A. Yogi, R. C. Tostes, E. Legros, P. D'Orleans-Juste, V. L. Lanchote, S. A. Uyemura, and A. M. de Oliveira Ethanol Consumption Enhances Endothelin-1-Induced Contraction in the Isolated Rat Carotid J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 819 - 827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Battistini, N. Berthiaume, N. F. Kelland, D. J. Webb, and D. E. Kohan Profile of Past and Current Clinical Trials Involving Endothelin Receptor Antagonists: The Novel "-Sentan" Class of Drug. Experimental Biology and Medicine, June 1, 2006; 231(6): 653 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Dhaun, J. Goddard, and DavidJ. Webb The Endothelin System and Its Antagonism in Chronic Kidney Disease J. Am. Soc. Nephrol., April 1, 2006; 17(4): 943 - 955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Potenza, F. L. Marasciulo, D. M. Chieppa, G. S. Brigiani, G. Formoso, M. J. Quon, and M. Montagnani Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H813 - H822. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Lahav, M.-L. Suva, D. Rimoldi, P. H. Patterson, and I. Stamenkovic Endothelin Receptor B Inhibition Triggers Apoptosis and Enhances Angiogenesis in Melanomas Cancer Res., December 15, 2004; 64(24): 8945 - 8953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Campia, C. Cardillo, and J. A. Panza Ethnic Differences in the Vasoconstrictor Activity of Endogenous Endothelin-1 in Hypertensive Patients Circulation, June 29, 2004; 109(25): 3191 - 3195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Cardillo, U. Campia, M. Iantorno, and J. A. Panza Enhanced Vascular Activity of Endogenous Endothelin-1 in Obese Hypertensive Patients Hypertension, January 1, 2004; 43(1): 36 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Lawrenson, J. G. Poole, J. Kim, C. Brown, P. Patel, and R. S. Richardson Vascular and metabolic response to isolated small muscle mass exercise: effect of age Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1023 - H1031. [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]
|
|
|
|
|
|
A. Nohria, L. Garrett, W. Johnson, S. Kinlay, P. Ganz, and M. A. Creager Endothelin-1 and Vascular Tone in Subjects With Atherogenic Risk Factors Hypertension, July 1, 2003; 42(1): 43 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Suga, N. Yasui, F. Yoshihara, T. Horio, Y. Kawano, K. Kangawa, and R. J. Johnson Endothelin A Receptor Blockade and Endothelin B Receptor Blockade Improve Hypokalemic Nephropathy by Different Mechanisms J. Am. Soc. Nephrol., February 1, 2003; 14(2): 397 - 406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Rossi, C. Ganzaroli, M. Cesari, A. Maresca, M. Plebani, G. G. Nussdorfer, and A. C. Pessina Endothelin receptor blockade lowers plasma aldosterone levels via different mechanisms in primary aldosteronism and high-to-normal renin hypertension Cardiovasc Res, January 1, 2003; 57(1): 277 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Cardillo, U. Campia, M. B. Bryant, and J. A. Panza Increased Activity of Endogenous Endothelin in Patients With Type II Diabetes Mellitus Circulation, October 1, 2002; 106(14): 1783 - 1787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Goddard, D. J. Webb, P. Martin, and H. Krum Endothelin Antagonists and Hypertension: A Question of Dose? * Response Hypertension, September 1, 2002; e2(3): . [Full Text] [PDF]
|
|
|
|
|
|
W. Johnson, A. Nohria, L. Garrett, J. C. Fang, J. Igo, M. Katai, P. Ganz, and M. A. Creager Contribution of endothelin to pulmonary vascular tone under normoxic and hypoxic conditions Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H568 - H575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. McEniery, I. B. Wilkinson, D. G. Jenkins, and D. J. Webb Endogenous Endothelin-1 Limits Exercise-Induced Vasodilation in Hypertensive Humans Hypertension, August 1, 2002; 40(2): 202 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Bohm, G. Ahlborg, B.-L. Johansson, L.-O. Hansson, and J. Pernow Combined Endothelin Receptor Blockade Evokes Enhanced Vasodilatation in Patients With Atherosclerosis Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 674 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. H.S. Kim and L. J. Rubin Endothelin in Health and Disease: Endothelin Receptor Antagonists in the Management of Pulmonary Artery Hypertension Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2002; 7(1): 9 - 19. [Abstract] [PDF]
|
|
|
|
 |
|
 A. V Agapitov and W. G Haynes Role of endothelin in cardiovascular disease Journal of Renin-Angiotensin-Aldosterone System, March 1, 2002; 3(1): 1 - 15. [Abstract] [PDF]
|
|
|
|
|
|
P. Martin, D. Ninio, and H. Krum Effect of Endothelin Blockade on Basal and Stimulated Forearm Blood Flow in Patients With Essential Hypertension Hypertension, March 1, 2002; 39(3): 821 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Montanari, N. Carra, P. Perinotto, V. Iori, E. Fasoli, A. Biggi, and A. Novarini Renal Hemodynamic Control by Endothelin and Nitric Oxide Under Angiotensin II Blockade in Man Hypertension, February 1, 2002; 39(2): 715 - 720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Cardillo, U. Campia, C. M. Kilcoyne, M. B. Bryant, and J. A. Panza Improved Endothelium-Dependent Vasodilation After Blockade of Endothelin Receptors in Patients With Essential Hypertension Circulation, January 29, 2002; 105(4): 452 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Panza High-Normal Blood Pressure -- More "High" Than "Normal" N. Engl. J. Med., November 1, 2001; 345(18): 1337 - 1340. [Full Text] [PDF]
|
|
|
|
 |
|
 F. A Dinenno, H. Tanaka, B. L Stauffer, and D. R Seals Reductions in basal limb blood flow and vascular conductance with human ageing: role for augmented {alpha}-adrenergic vasoconstriction J. Physiol., November 1, 2001; 536(3): 977 - 983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Ballew and G. D. Fink Role of endothelin ETB receptor activation in angiotensin II-induced hypertension: effects of salt intake Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H2218 - H2225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kinlay, D. Behrendt, M. Wainstein, J. Beltrame, J. C. Fang, M. A. Creager, A. P. Selwyn, and P. Ganz Role of Endothelin-1 in the Active Constriction of Human Atherosclerotic Coronary Arteries Circulation, September 4, 2001; 104(10): 1114 - 1118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Asai, R. K. Kudej, G. Takagi, A. B. Kudej, F. Natividad, Y.-T. Shen, D. E. Vatner, and S. F. Vatner Paradoxically Enhanced Endothelin-B Receptor-Mediated Vasoconstriction in Conscious Old Monkeys Circulation, May 15, 2001; 103(19): 2382 - 2386. [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]
|
|
|
|
 |
|
 C. Cardillo, C. M. Kilcoyne, R. O. Cannon III, and J. A. Panza Increased activity of endogenous endothelin in patients with hypercholesterolemia J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1483 - 1488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Barton, L. V. d'Uscio, Y. Hirata, M. Kakoki, H. Hayakawa, A. Tojo, D. Nagata, E. Suzuki, K. Kimura, A. Goto, et al. Hypertension, Diabetes Mellitus, Hypercholesterolemia, and Endothelin B Receptor-Mediated Renal Nitric Oxide Release Response Circulation, June 13, 2000; 101 (23): e228 - e229. [Full Text] [PDF]
|
|
|
|
|
|
C. Cardillo, C. M. Kilcoyne, R. O. Cannon III, and J. A. Panza Interactions Between Nitric Oxide and Endothelin in the Regulation of Vascular Tone of Human Resistance Vessels In Vivo Hypertension, June 1, 2000; 35(6): 1237 - 1241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ghiadoni, A. Virdis, A. Magagna, S. Taddei, and A. Salvetti Effect of the Angiotensin II Type 1 Receptor Blocker Candesartan on Endothelial Function in Patients With Essential Hypertension Hypertension, January 1, 2000; 35(1): 501 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Montanari, A. Biggi, N. Carra, E. Fasoli, M. Calzolari, F. Corsini, P. Perinotto, and A. Novarini Endothelin-A Blockade Attenuates Systemic and Renal Hemodynamic Effects of L-NAME in Humans Hypertension, January 1, 2000; 35(1): 518 - 523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Taddei, A. Virdis, L. Ghiadoni, I. Sudano, M. Notari, and A. Salvetti Vasoconstriction to Endogenous Endothelin-1 Is Increased in the Peripheral Circulation of Patients With Essential Hypertension Circulation, October 19, 1999; 100(16): 1680 - 1683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin Role of Endothelin-1 in Hypertension Hypertension, October 1, 1999; 34(4): 876 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Cardillo, S. S. Nambi, C. M. Kilcoyne, W. K. Choucair, A. Katz, M. J. Quon, and J. A. Panza Insulin Stimulates Both Endothelin and Nitric Oxide Activity in the Human Forearm Circulation, August 24, 1999; 100(8): 820 - 825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
F. Bohm, G. Ahlborg, B.-L. Johansson, L.-O. Hansson, and J. Pernow Combined Endothelin Receptor Blockade Evokes Enhanced Vasodilatation in Patients With Atherosclerosis Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 674 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Brook, J. R. Brook, B. Urch, R. Vincent, S. Rajagopalan, and F. Silverman Inhalation of Fine Particulate Air Pollution and Ozone Causes Acute Arterial Vasoconstriction in Healthy Adults Circulation, April 2, 2002; 105(13): 1534 - 1536. [Abstract] [Full Text] [PDF]
|
|