(Hypertension. 1999;34:296-301.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Angiotensin-(1–7) Is a Modulator of the Human Renin-Angiotensin System
From the Department of Clinical Pharmacology, University of Groningen (Netherlands).
Correspondence to A.J.M. Roks, Department of Clinical Pharmacology, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, Netherlands. E-mail a.j.m.roks{at}med.rug.nl
Abstract—The renin-angiotensin system is important for cardiovascular homeostasis. Currently, therapies for different cardiovascular diseases are based on inhibition of angiotensin-converting enzyme (ACE) or angiotensin II receptor blockade. Inhibition of ACE blocks metabolism of angiotensin-(1–7) to angiotensin-(1–5) and can lead to elevation of angiotensin-(1–7) levels in plasma and tissue. In animal models, angiotensin-(1–7) itself causes or enhances vasodilation and inhibits vascular contractions to angiotensin II. The function of angiotensin-(1–5) is unknown. We investigated whether angiotensin-(1–7) and angiotensin-(1–5) inhibit ACE or antagonize angiotensin-induced vasoconstrictions in humans. ACE activity in plasma and atrial tissue was inhibited by angiotensin-(1–7) up to 100%, with an IC50 of 3.0 and 4.0 µmol/L, respectively. In human internal mammary arteries, contractions induced by angiotensin I and II and the non–ACE-specific substrate [Pro11,D-Ala12]-angiotensin I were antagonized by angiotensin-(1–7) (10-5 mol/L) in a noncompetitive way, with a 60% inhibition of the maximal response to angiotensin II. Contractions to ACE-specific substrate [Pro10]-angiotensin I were also inhibited, an effect only partly accounted for by antagonism of angiotensin II. Angiotensin-(1–5) inhibited plasma ACE activity with a potency equal to that of angiotensin I but had no effect on arterial contractions. In conclusion, angiotensin-(1–7) blocks angiotensin II–induced vasoconstriction and inhibits ACE in human cardiovascular tissues. Angiotensin-(1–5) only inhibits ACE. These results show that angiotensin-(1–7) may be an important modulator of the human renin-angiotensin system.
Key Words: angiotensin-(1–7) • angiotensin-(1–5) • angiotensin I • angiotensin II • angiotensin-converting enzyme • chymase • arteries
This article has been cited by other articles:
 |
|
 |
|
  J. M. Stewart, A. J. Ocon, D. Clarke, I. Taneja, and M. S. Medow Defects in Cutaneous Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7) Production in Postural Tachycardia Syndrome Hypertension, May 1, 2009; 53(5): 767 - 774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D. Kluskens, S. A. Nelemans, R. Rink, L. de Vries, A. Meter-Arkema, Y. Wang, T. Walther, A. Kuipers, G. N. Moll, and M. Haas Angiotensin-(1-7) with Thioether Bridge: An Angiotensin-Converting Enzyme-Resistant, Potent Angiotensin-(1-7) Analog J. Pharmacol. Exp. Ther., March 1, 2009; 328(3): 849 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. O. Sampaio, C. Henrique de Castro, R. A.S. Santos, E. L. Schiffrin, and R. M. Touyz Angiotensin-(1-7) Counterregulates Angiotensin II Signaling in Human Endothelial Cells Hypertension, December 1, 2007; 50(6): 1093 - 1098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Keidar, M. Kaplan, and A. Gamliel-Lazarovich ACE2 of the heart: From angiotensin I to angiotensin (1-7) Cardiovasc Res, February 1, 2007; 73(3): 463 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Reyes-Engel, L. Morcillo, F. J. Aranda, M. Ruiz, M. J. Gaitan, A. Mayor-Olea, P. Aranda, and C. M. Ferrario Influence of Gender and Genetic Variability on Plasma Angiotensin Peptides Journal of Renin-Angiotensin-Aldosterone System, June 1, 2006; 7(2): 92 - 97. [Abstract] [PDF]
|
|
|
|
|
|
M. K. Raizada and S. D. Sarkissian Potential of Gene Therapy Strategy for the Treatment of Hypertension Hypertension, January 1, 2006; 47(1): 6 - 9. [Full Text] [PDF]
|
|
|
|
 |
|
 G Paizis, C Tikellis, M E Cooper, J M Schembri, R A Lew, A I Smith, T Shaw, F J Warner, A Zuilli, L M Burrell, et al. Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2 Gut, December 1, 2005; 54(12): 1790 - 1796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A van der Wouden, R. H Henning, L. E Deelman, A. J. Roks, F. Boomsma, and D. de Zeeuw Does Angiotensin (1-7) Contribute to the Antiproteinuric Effect of ACE-inhibitors? Journal of Renin-Angiotensin-Aldosterone System, June 1, 2005; 6(2): 96 - 101. [Abstract] [PDF]
|
|
|
|
 |
|
 M. J. Katovich, J. L. Grobe, M. Huentelman, and M. K. Raizada Angiotensin-converting enzyme 2 as a novel target for gene therapy for hypertension Exp Physiol, May 1, 2005; 90(3): 299 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H.M. van Esch, B. Tom, V. Dive, W. W. Batenburg, D. Georgiadis, A. Yiotakis, J. M.G. van Gool, R. J.A. de Bruijn, R. de Vries, and A.H. J. Danser Selective Angiotensin-Converting Enzyme C-Domain Inhibition Is Sufficient to Prevent Angiotensin I-Induced Vasoconstriction Hypertension, January 1, 2005; 45(1): 120 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Zhong, D.-Y. Huang, Y.-M. Yang, Y.-F. Li, G.-F. Liu, X.-H. Song, and K. Du Upregulation of Angiotensin-Converting Enzyme 2 by All-trans Retinoic Acid in Spontaneously Hypertensive Rats Hypertension, December 1, 2004; 44(6): 907 - 912. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Rosas-Vargas, R. M. Coral-Vazquez, R. Tapia, J. L. Borja, R. A. Salas, and F. Salamanca Glu298Asp Endothelial Nitric Oxide Synthase Polymorphism Is a Risk Factor for Erectile Dysfunction in the Mexican Mestizo Population J Androl, September 1, 2004; 25(5): 728 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Stegbauer, V. Oberhauser, O. Vonend, and L. C. Rump Angiotensin-(1-7) modulates vascular resistance and sympathetic neurotransmission in kidneys of spontaneously hypertensive rats Cardiovasc Res, February 1, 2004; 61(2): 352 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. S. Santos, A. C. S. e Silva, C. Maric, D. M. R. Silva, R. P. Machado, I. de Buhr, S. Heringer-Walther, S. V. B. Pinheiro, M. T. Lopes, M. Bader, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas PNAS, July 8, 2003; 100(14): 8258 - 8263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Schmaier The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2003; 285(1): R1 - R13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Haulica, W. Bild, C. N Mihaila, T. Ionita, C. P Boisteanu, and B. Neagu Biphasic effects of angiotensin (1-7) and its interactions with angiotensin II in rat aorta Journal of Renin-Angiotensin-Aldosterone System, June 1, 2003; 4(2): 124 - 128. [Abstract] [PDF]
|
|
|
|
 |
|
 W. O. Sampaio, A. A. S. Nascimento, and R. A. S. Santos Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting Enzyme Systems: Systemic and regional hemodynamic effects of angiotensin-(1-7) in rats Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H1985 - H1994. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wiemer, L. W. Dobrucki, F. R. Louka, T. Malinski, and H. Heitsch AVE 0991, a Nonpeptide Mimic of the Effects of Angiotensin-(1-7) on the Endothelium Hypertension, December 1, 2002; 40(6): 847 - 852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. McMurray, A. P. Davie, A. E. Loot, A. J.M. Roks, R. H. Henning, W. H. van Gilst, R. A. Tio, A. J.H. Suurmeyer, and F. Boomsma Angiotensin-(1-7) Attenuates the Development of Heart Failure After Myocardial Infarction in Rats * Response Circulation, November 12, 2002; 106 (20): e147 - e147. [Full Text] [PDF]
|
|
|
|
|
|
I. Kucharewicz, R. Pawlak, T. Matys, D. Pawlak, and W. Buczko Antithrombotic Effect of Captopril and Losartan Is Mediated by Angiotensin-(1-7) Hypertension, November 1, 2002; 40(5): 774 - 779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. F. van Rodijnen, T. A. van Lambalgen, M. H. van Wijhe, G.-J. Tangelder, and P. M. ter Wee Renal microvascular actions of angiotensin II fragments Am J Physiol Renal Physiol, July 1, 2002; 283(1): F86 - F92. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-C. Wei, C. M. Ferrario, K. B. Brosnihan, D. M. Farrell, W. E. Bradley, A. A. Jaffa, and L. J. Dell'Italia Angiotensin Peptides Modulate Bradykinin Levels in the Interstitium of the Dog Heart in Vivo J. Pharmacol. Exp. Ther., January 1, 2002; 300(1): 324 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Souza dos Santos, K. T. Passaglio, J. B. Pesquero, M. Bader, and A. C. Simoes e Silva Interactions Between Angiotensin-(1-7), Kinins, and Angiotensin II in Kidney and Blood Vessels Hypertension, September 1, 2001; 38(3): 660 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Tom, R. de Vries, P. R. Saxena, and A.H. J. Danser Bradykinin Potentiation by Angiotensin-(1-7) and ACE Inhibitors Correlates With ACE C- and N-Domain Blockade Hypertension, July 1, 2001; 38(1): 95 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Wilsdorf, J. V. Gainer, L. J. Murphey, D. E. Vaughan, and N. J. Brown Angiotensin-(1-7) Does Not Affect Vasodilator or TPA Responses to Bradykinin in Human Forearm Hypertension, April 1, 2001; 37(4): 1136 - 1140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Clark, D. I. Diz, and E. A. Tallant Angiotensin-(1-7) Downregulates the Angiotensin II Type 1 Receptor in Vascular Smooth Muscle Cells Hypertension, April 1, 2001; 37(4): 1141 - 1146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Heitsch, S. Brovkovych, T. Malinski, and G. Wiemer Angiotensin-(1-7)-Stimulated Nitric Oxide and Superoxide Release From Endothelial Cells Hypertension, January 1, 2001; 37(1): 72 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Allred, D. I. Diz, C. M. Ferrario, and M. C. Chappell Pathways for angiotensin-(1---7) metabolism in pulmonary and renal tissues Am J Physiol Renal Physiol, November 1, 2000; 279(5): F841 - F850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Loot, A. J.M. Roks, R. H. Henning, R. A. Tio, A. J.H. Suurmeijer, F. Boomsma, and W. H. van Gilst Angiotensin-(1-7) Attenuates the Development of Heart Failure After Myocardial Infarction in Rats Circulation, April 2, 2002; 105(13): 1548 - 1550. [Abstract] [Full Text] [PDF]
|
|