(Circulation. 1997;96:1593-1597.)
© 1997 American Heart Association, Inc.
Articles |
From Cardiology, Cardiovascular Research, and Division of Hypertension (S.S.), University Hospital, Bern, and Cardiology, University Hospital, Zürich, Switzerland.
Correspondence to Thomas F. Lüscher, MD, FACC, FESC, Professor and Head of Cardiology, University Hospital, CH-8091 Zürich, Switzerland. E-mail 100771.1237{at}compuserve.com
Background In vitro studies on vascular smooth muscle cells suggest that endothelin has a stimulating effect on cellular proliferation. This study was designed to determine the endogenous effect of endothelin on angiotensin IIinduced hypertrophy of small arteries in vivo.
Methods and Results Two weeks of angiotensin II administration (200 ng·kg-1·min-1) increased media thickness, media/lumen ratio, and cross-sectional area of basilar and small mesenteric arteries, confirming the proliferative properties of angiotensin II. The tissue levels of endothelin-1 were elevated in mesenteric arteries after angiotensin II administration. The administration of the selective and specific ETA-receptor antagonist LU135252 (50 mg·kg-1·d-1) in combination with angiotensin II prevented the changes of vascular geometry and partially reduced the increase in blood pressure induced by angiotensin II. Indeed, part of the effect on the vascular structure of the endothelin-receptor antagonist seemed pressure-independent.
Conclusions Our results therefore demonstrate that angiotensin II increases the production of endothelin in the blood vessel wall that, via ETA receptors, mediates changes in vascular structure of the cerebral and mesenteric circulation. Endothelin antagonists may therefore be of value to reduce blood pressure and to prevent vascular structural changes in conditions of increased activity of the renin-angiotensin system.
Key Words: angiotensin endothelin receptors arteries
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D. P. Wilson, L. Saward, P. Zahradka, and P. Kee Cheung Angiotensin II receptor antagonists prevent neointimal proliferation in a porcine coronary artery organ culture model Cardiovasc Res, June 1, 1999; 42(3): 761 - 772. [Abstract] [Full Text] [PDF] |
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K. Munter, H. Ehmke, and M. Kirchengast Maintenance of blood pressure in normotensive dogs by endothelin Am J Physiol Heart Circ Physiol, March 1, 1999; 276(3): H1022 - H1027. [Abstract] [Full Text] [PDF] |
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B. Hocher, I. George, J. Rebstock, A. Bauch, A. Schwarz, H.-H. Neumayer, and C. Bauer Endothelin System–Dependent Cardiac Remodeling in Renovascular Hypertension Hypertension, March 1, 1999; 33(3): 816 - 822. [Abstract] [Full Text] [PDF] |
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F. C. Luft, E. Mervaala, D. N. Muller, V. Gross, F. Schmidt, J. K. Park, C. Schmitz, A. Lippoldt, V. Breu, R. Dechend, et al. Hypertension-Induced End-Organ Damage : A New Transgenic Approach to an Old Problem Hypertension, January 1, 1999; 33(1): 212 - 218. [Abstract] [Full Text] [PDF] |
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P. Moreau Endothelin in hypertension: A role for receptor antagonists? Cardiovasc Res, September 1, 1998; 39(3): 534 - 542. [Abstract] [Full Text] [PDF] |
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T. J Rabelink, E. S.G Stroes, K.P. Bouter, and P. Morrison Endothelin blockers and renal protection: a new strategy to prevent end-organ damage in cardiovascular disease? Cardiovasc Res, September 1, 1998; 39(3): 543 - 549. [Full Text] [PDF] |
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M. Kirchengast and K. Munter Endothelin and restenosis Cardiovasc Res, September 1, 1998; 39(3): 550 - 555. [Full Text] [PDF] |
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L. V. d'Uscio, S. Shaw, M. Barton, and T. F. Luscher Losartan but Not Verapamil Inhibits Angiotensin II–Induced Tissue Endothelin-1 Increase : Role of Blood Pressure and Endothelial Function Hypertension, June 1, 1998; 31(6): 1305 - 1310. [Abstract] [Full Text] [PDF] |
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P. Moreau, H. Takase, L. V. d'Uscio, T. F. Luscher, and G. L. Baumbach Effect of Chronic Nitric Oxide Deficiency on Angiotensin II–Induced Hypertrophy of Rat Basilar Artery • Editorial Comment Stroke, May 1, 1998; 29(5): 1031 - 1036. [Abstract] [Full Text] [PDF] |
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M. Barton, L. V. d'Uscio, S. Shaw, P. Meyer, P. Moreau, and T. F. Luscher ETA Receptor Blockade Prevents Increased Tissue Endothelin-1, Vascular Hypertrophy, and Endothelial Dysfunction in Salt-Sensitive Hypertension Hypertension, January 1, 1998; 31(1): 499 - 504. [Abstract] [Full Text] [PDF] |
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L. Moser, J. Faulhaber, R. J. Wiesner, and H. Ehmke Predominant activation of endothelin-dependent cardiac hypertrophy by norepinephrine in rat left ventricle Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2002; 282(5): R1389 - R1394. [Abstract] [Full Text] [PDF] |
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