doi: 10.1161/hc0502.102965
(Circulation. 2002;105:627.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Induction of Functional Bradykinin B1-Receptors in Normotensive Rats and Mice Under Chronic Angiotensin-Converting Enzyme Inhibitor Treatment
From the Institut National de la Santé et de la Recherche Médicale INSERM U 388, Institut Louis Bugnard, CHU Rangueil, Toulouse, France.
Correspondence to J.P. Girolami, INSERM U388, Institut Louis Bugnard, CHU Rangueil, 31403 Toulouse Cedex, France. E-mail girolami{at}toulouse.inserm.fr
Background— The physiological effects of ACE inhibitors may act in part through a kinin-dependent mechanism. We investigated the effect of chronic ACE-inhibitor treatment on functional kinin B1- and B2-receptor expression, which are the molecular entities responsible for the biological effects of kinins.
Methods and Results— Rats were subjected to different 6-week treatments using various mixtures of the following agents: ACE inhibitor, angiotensin AT1-receptor antagonist, and B1- and B2-receptor antagonists. Chronic ACE inhibition induced both renal and vascular B1-receptor expression, whereas B2-receptor expression was not modified. Furthermore, with B1-receptor antagonists, it was shown that B1-receptor induction was involved in the hypotensive effect of ACE inhibition. Using microdissection, we prepared 10 different nephron segments and found ACE-inhibitor–induced expression of functional B1-receptors in all segments. ACE-inhibitor–induced B1-receptor induction involved homologous upregulation, because it was prevented by B1-receptor antagonist treatment. Finally, using B2-receptor knockout mice, we showed that ACE-inhibitor–induced B1-receptor expression was B2-receptor independent.
Conclusions— This study provides the first evidence that chronic ACE-inhibitor administration is associated with functional vascular and renal B1-receptor induction, which is involved in ACE-inhibitor–induced hypotension. The observed B1-receptor induction in the kidney might participate in the known renoprotective effects of ACE inhibition.
Key Words: angiotensin-converting enzyme • bradykinin • kidney • blood pressure
This article has been cited by other articles:
 |
|
 |
|
  J. Allard, M. Buleon, E. Cellier, I. Renaud, C. Pecher, F. Praddaude, M. Conti, I. Tack, and J.-P. Girolami ACE inhibitor reduces growth factor receptor expression and signaling but also albuminuria through B2-kinin glomerular receptor activation in diabetic rats Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1083 - F1092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Moreau, P. Dubreuil, G. Molinaro, M. Chagnon, W. Muller-Esterl, Y. Lepage, F. Marceau, and A. Adam Expression of Metallopeptidases and Kinin Receptors in Swine Oropharyngeal Tissues: Effects of Angiotensin I-Converting Enzyme Inhibition and Inflammation J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1065 - 1074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Oliver, D. J. Webb, and D. E. Newby Stimulated Tissue Plasminogen Activator Release as a Marker of Endothelial Function in Humans Arterioscler. Thromb. Vasc. Biol., December 1, 2005; 25(12): 2470 - 2479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Picard, M. Van Abel, C. Campone, M. Seiler, M. Bloch-Faure, J. G.J. Hoenderop, J. Loffing, P. Meneton, R. J.M. Bindels, M. Paillard, et al. Tissue Kallikrein-Deficient Mice Display a Defect in Renal Tubular Calcium Absorption J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3602 - 3610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-P. Fortin, L. Gera, J. Bouthillier, J. M. Stewart, A. Adam, and F. Marceau Endogenous Aminopeptidase N Decreases the Potency of Peptide Agonists and Antagonists of the Kinin B1 Receptors in the Rabbit Aorta J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1169 - 1176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Tiwari, P. L. Prather, and P. R. Mayeux Mechanism of Bradykinin-Induced Ca2+ Mobilization in Murine Proximal Tubule Epithelial Cells J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 798 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Liesmaa, A. Kuoppala, N. Shiota, J. O. Kokkonen, K. Kostner, M. Mayranpaa, P. T. Kovanen, and K. A. Lindstedt Increased expression of bradykinin type-1 receptors in endothelium of intramyocardial coronary vessels in human failing hearts Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2317 - H2322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L.M. Cruden, G. H. Tse, K. A.A. Fox, C. A. Ludlam, I. Megson, and D. E. Newby B1 Kinin Receptor Does Not Contribute to Vascular Tone or Tissue Plasminogen Activator Release in the Peripheral Circulation of Patients With Heart Failure Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 772 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. F. Leeb-Lundberg, F. Marceau, W. Muller-Esterl, D. J. Pettibone, and B. L. Zuraw International Union of Pharmacology. XLV. Classification of the Kinin Receptor Family: from Molecular Mechanisms to Pathophysiological Consequences Pharmacol. Rev., March 1, 2005; 57(1): 27 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L.M. Cruden, K. A.A. Fox, C. A. Ludlam, N. R. Johnston, and D. E. Newby Neutral Endopeptidase Inhibition Augments Vascular Actions of Bradykinin in Patients Treated With Angiotensin-Converting Enzyme Inhibition Hypertension, December 1, 2004; 44(6): 913 - 918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ignjatovic, S. Stanisavljevic, V. Brovkovych, R. A. Skidgel, and E. G. Erdos Kinin B1 Receptors Stimulate Nitric Oxide Production in Endothelial Cells: Signaling Pathways Activated by Angiotensin I-Converting Enzyme Inhibitors and Peptide Ligands Mol. Pharmacol., November 1, 2004; 66(5): 1310 - 1316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Sulpizio, M. A. Pullen, R. M. Edwards, and D. P. Brooks The Effect of Acute Angiotensin-Converting Enzyme and Neutral Endopeptidase 24.11 Inhibition on Plasma Extravasation in the Rat J. Pharmacol. Exp. Ther., June 1, 2004; 309(3): 1141 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L.M. Cruden, F. N. Witherow, D. J. Webb, K. A.A. Fox, and D. E. Newby Bradykinin Contributes to the Systemic Hemodynamic Effects of Chronic Angiotensin-Converting Enzyme Inhibition in Patients With Heart Failure Arterioscler. Thromb. Vasc. Biol., June 1, 2004; 24(6): 1043 - 1048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Tschope, F. Spillmann, C. Altmann, M. Koch, D. Westermann, N. Dhayat, S. Dhayat, J.-L. Bascands, L. Gera, S. Hoffmann, et al. The bradykinin B1 receptor contributes to the cardioprotective effects of AT1 blockade after experimental myocardial infarction Cardiovasc Res, February 15, 2004; 61(3): 559 - 569. [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]
|
|
|
|
|
|
T.N. Dzeka, R. Townley, and J.M. O. Arnold Effects of enalaprilat on venoconstriction to norepinephrine: role of prostaglandins Cardiovasc Res, July 1, 2003; 59(1): 250 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Skidgel, F. Alhenc-Gelas, and W. B. Campbell Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting Enzyme Systems: Prologue: Kinins and related systems. New life for old discoveries Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H1886 - H1891. [Full Text] [PDF]
|
|
|
|
|
|
J. P. Schanstra, J. Duchene, F. Praddaude, P. Bruneval, I. Tack, J. Chevalier, J.-P. Girolami, and J.-L. Bascands Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting Enzyme Systems: Decreased renal NO excretion and reduced glomerular tuft area in mice lacking the bradykinin B2 receptor Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H1904 - H1908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ongali, H. d. S. Buck, F. Cloutier, F. Legault, D. Regoli, C. Lambert, G. Thibault, and R. Couture Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting Enzyme Systems: Chronic effects of angiotensin-converting enzyme inhibition on kinin receptor binding sites in the rat spinal cord Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H1949 - H1958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sangsree, V. Brovkovych, R. D. Minshall, and R. A. Skidgel Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting Enzyme Systems: Kininase I-type carboxypeptidases enhance nitric oxide production in endothelial cells by generating bradykinin B1 receptor agonists Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H1959 - H1968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. D. Xiao, S. Fuchs, J. M. Cole, K. M. Disher, R. L. Sutliff, and K. E. Bernstein Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting-Enzyme Systems: Role of bradykinin in angiotensin-converting enzyme knockout mice Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H1969 - H1977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Molinaro, M. Cugno, M. Perez, Y. Lepage, N. Gervais, A. Agostoni, and A. Adam Angiotensin-Converting Enzyme Inhibitor-Associated Angioedema Is Characterized by a Slower Degradation of des-Arginine9-Bradykinin J. Pharmacol. Exp. Ther., October 1, 2002; 303(1): 232 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. N. Witherow, P. Dawson, C. A. Ludlam, K. A. A. Fox, and D. E. Newby Marked bradykinin-induced tissue plasminogen activator release in patients with heart failure maintained on long-term angiotensin-converting enzyme inhibitor therapy J. Am. Coll. Cardiol., September 4, 2002; 40(5): 961 - 966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Trabold, S. Pons, A. A. Hagege, M. Bloch-Faure, F. Alhenc-Gelas, J.-F. Giudicelli, C. Richer-Giudicelli, and P. Meneton Cardiovascular Phenotypes of Kinin B2 Receptor- and Tissue Kallikrein-Deficient Mice Hypertension, July 1, 2002; 40(1): 90 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ignjatovic, F. Tan, V. Brovkovych, R. A. Skidgel, and E. G. Erdos Novel Mode of Action of Angiotensin I Converting Enzyme Inhibitors. DIRECT ACTIVATION OF BRADYKININ B1 RECEPTOR J. Biol. Chem., May 3, 2002; 277(19): 16847 - 16852. [Abstract] [Full Text] [PDF]
|
|