(Hypertension. 2001;38:95.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Bradykinin Potentiation by Angiotensin-(1-7) and ACE Inhibitors Correlates With ACE C- and N-Domain Blockade
From the Department of Pharmacology, Erasmus University Rotterdam, The Netherlands.
Correspondence to A.H.J. Danser, PhD, Department of Pharmacology, Room EE1418b, Erasmus University Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail danser{at}farma.fgg.eur.nl
Abstract— ACE inhibitors block B2 receptor desensitization, thereby potentiating bradykinin beyond blocking its hydrolysis. Angiotensin (Ang)-(1-7) also acts as an ACE inhibitor and, in addition, may stimulate bradykinin release via angiotensin II type 2 receptors. In this study we compared the bradykinin-potentiating effects of Ang-(1-7), quinaprilat, and captopril. Porcine coronary arteries, obtained from 32 pigs, were mounted in organ baths, preconstricted with prostaglandin F2
, and exposed to quinaprilat, captopril, Ang-(1-7), and/or bradykinin. Bradykinin induced complete relaxation (pEC50=8.11±0.07, mean±SEM), whereas quinaprilat, captopril, and Ang-(1-7) alone were without effect. Quinaprilat shifted the bradykinin curve to the left in a biphasic manner: a 5-fold shift at concentrations that specifically block the C-domain (0.1 to 1 nmol/L) and a 10-fold shift at concentrations that block both domains. Captopril and Ang-(1-7) monophasically shifted the bradykinin curve to the left, by a factor of 10 and 5, respectively. A 5-fold shift was also observed when Ang-(1-7) was combined with 0.1 nmol/L quinaprilat. Repeated exposure of porcine coronary arteries to 0.1 µmol/L bradykinin induced B2 receptor desensitization. The addition of 10 µmol/L quinaprilat or Ang-(1-7) to the bath, at a time when bradykinin alone was no longer able to induce relaxation, fully restored the relaxant effects of bradykinin. Angiotensin II type 1 or 2 receptor blockade did not affect any of the observed effects of Ang-(1-7). In conclusion, Ang-(1-7), like quinaprilat and captopril, potentiates bradykinin by acting as an ACE inhibitor. Bradykinin potentiation is maximal when both the ACE C- and N-terminal domains are inhibited. The inhibitory effects of Ang-(1-7) are limited to the ACE C-domain, raising the possibility that Ang-(1-7) synergistically increases the blood pressure-lowering effects of N-domain-specific ACE inhibitors.
Key Words: angiotensin • bradykinin • angiotensin-converting enzyme inhibitors • receptors, bradykinin • coronary artery
This article has been cited by other articles:
 |
|
 |
|
  Kaiqiang Ji, M. Minakawa, K. Fukui, Y. Suzuki, and I. Fukuda Olmesartan improves left ventricular function in pressure-overload hypertrophied rat heart by blocking angiotensin II receptor with synergic effects of upregulation of angiotensin converting enzyme 2 Therapeutic Advances in Cardiovascular Disease, April 1, 2009; 3(2): 103 - 111. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Oeseburg, D. Iusuf, P. van der Harst, W. H. van Gilst, R. H. Henning, and A. J.M. Roks Bradykinin Protects Against Oxidative Stress-Induced Endothelial Cell Senescence Hypertension, February 1, 2009; 53(2): 417 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Reudelhuber A Place in Our Hearts for the Lowly Angiotensin 1-7 Peptide? Hypertension, May 1, 2006; 47(5): 811 - 815. [Full Text] [PDF]
|
|
|
|
 |
|
 I. Fleming Signaling by the Angiotensin-Converting Enzyme Circ. Res., April 14, 2006; 98(7): 887 - 896. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 B. Tom, I. M. Garrelds, E. Scalbert, A. P.A. Stegmann, F. Boomsma, P. R. Saxena, and A.H. J. Danser ACE- Versus Chymase-Dependent Angiotensin II Generation in Human Coronary Arteries: A Matter of Efficiency? Arterioscler Thromb Vasc Biol, February 1, 2003; 23(2): 251 - 256. [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]
|
|
|
|
 |
|
 E. G Erdos Kinins, the long march--A personal view Cardiovasc Res, June 1, 2002; 54(3): 485 - 491. [Full Text] [PDF]
|
|
|
|
|
|
P. A. Deddish, B. M. Marcic, F. Tan, H. L. Jackman, Z. Chen, and E. G. Erdos Neprilysin Inhibitors Potentiate Effects of Bradykinin on B2 Receptor Hypertension, February 1, 2002; 39(2): 619 - 623. [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]
|
|