Published online before print March 27, 2006, doi: 10.1161/01.HYP.0000215289.51180.5c
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2006;47:996.)
© 2006 American Heart Association, Inc.
Original Articles |
Impairment of In Vitro and In Vivo Heart Function in Angiotensin-(1-7) Receptor Mas Knockout Mice
From the Departments of Physiology and Biophysics (R.A.S.S., C.H.C., A.P.A., R.D.d.P.), Morphology (E.G., G.T.K., A.J.F.), and Biochemistry and Immunology (J.S.C., A.S.R.), Biological Sciences Institute, Belo Horizonte, MG, Brazil; Department of Pediatrics (S.V.B.P.), Federal University of Minas Gerais, Belo Horizonte, MG, Brazil; Hypertension Unit (K.T.R., M.C.I.), Heart Institute, University of Sao Paulo, Sao Paulo, Brazil; and Max-Delbrück-Center for Molecular Medicine (M.B., N.A.), Berlin-Buch, Germany.
Correspondence to Robson A.S. Santos, Departments of Physiology and Biophysics, Av. Antônio Carlos, 6627 Biological Sciences Institute, UFMG, 31 270-901 Belo Horizonte, MG, Brazil. E-mail marrob{at}ciclope.Lcc.ufmg.br
In this study we investigated the effects of the genetic deletion of the angiotensin (Ang)-(1-7) receptor Mas on heart function. Localization of Mas in the mouse heart was evaluated by binding of rhodamine-labeled Ang-(1-7). Cardiac function was examined using isolated heart preparations. Echocardiography was used to confirm the results obtained with isolated heart studies. To elucidate the possible mechanisms involved in the cardiac phenotype observed in Mas–/– mice, whole-cell calcium currents in cardiomyocytes and the expression of collagen types I, III, and VI and fibronectin were analyzed. Ang-(1-7) binding showed that Mas is localized in cardiomyocytes of the mouse heart. Isolated heart techniques revealed that Mas-deficient mice present a lower systolic tension (average: 1.4±0.09 versus 2.1±0.03 g in Mas+/+ mice), ±dT/dt, and heart rate. A significantly higher coronary vessel resistance was also observed in Mas-deficient mice. Echocardiography revealed that hearts of Mas-deficient mice showed a significantly decreased fractional shortening, posterior wall thickness in systole and left ventricle end-diastolic dimension, and a higher left ventricle end-systolic dimension. A markedly lower global ventricular function, as defined by a higher myocardial performance index, was observed. A higher delayed time to the peak of calcium current was also observed. The changes in cardiac function could be partially explained by a marked change in collagen expression to a profibrotic profile in Mas-deficient mice. These results indicate that Ang-(1-7)-Mas axis plays a key role in the maintenance of the structure and function of the heart.
Key Words: receptors, angiotensin • extracellular matrix • echocardiography • heart failure • cardiac function
This article has been cited by other articles:
 |
|
 |
|
  J. Zimpelmann and K. D. Burns Angiotensin-(1-7) activates growth-stimulatory pathways in human mesangial cells Am J Physiol Renal Physiol, February 1, 2009; 296(2): F337 - F346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Stewart Jr, E. Lazartigues, and P. A. Lucchesi The Angiotensin Converting Enzyme 2/Ang-(1-7) Axis in the Heart: A Role for Mas Communication? Circ. Res., November 21, 2008; 103(11): 1197 - 1199. [Full Text] [PDF]
|
|
|
|
|
|
C. Mercure, A. Yogi, G. E. Callera, A. B. Aranha, M. Bader, A. J. Ferreira, R. A. S. Santos, T. Walther, R. M. Touyz, and T. L. Reudelhuber Angiotensin(1-7) Blunts Hypertensive Cardiac Remodeling by a Direct Effect on the Heart Circ. Res., November 21, 2008; 103(11): 1319 - 1326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Rentzsch, M. Todiras, R. Iliescu, E. Popova, L. A. Campos, M. L. Oliveira, O. C. Baltatu, R. A. Santos, and M. Bader Transgenic Angiotensin-Converting Enzyme 2 Overexpression in Vessels of SHRSP Rats Reduces Blood Pressure and Improves Endothelial Function Hypertension, November 1, 2008; 52(5): 967 - 973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Dias-Peixoto, R. A.S. Santos, E. R.M. Gomes, M. N.M. Alves, P. W.M. Almeida, L. Greco, M. Rosa, B. Fauler, M. Bader, N. Alenina, et al. Molecular Mechanisms Involved in the Angiotensin-(1-7)/Mas Signaling Pathway in Cardiomyocytes Hypertension, September 1, 2008; 52(3): 542 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Filho, A. J. Ferreira, S. H. S. Santos, S. R. S. Neves, E. R. Silva Camargos, L. K. Becker, H. A. Belchior, M. F. Dias-Peixoto, S. V. B. Pinheiro, and R. A. S. Santos Selective increase of angiotensin(1-7) and its receptor in hearts of spontaneously hypertensive rats subjected to physical training Exp Physiol, May 1, 2008; 93(5): 589 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Pan, C.-H. Wen, and C.-S. Lin Interplay of angiotensin II and angiotensin(1-7) in the regulation of matrix metalloproteinases of human cardiocytes Exp Physiol, May 1, 2008; 93(5): 599 - 612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. S. Santos, A. J. Ferreira, and A. C. Simoes e Silva Recent advances in the angiotensin-converting enzyme 2-angiotensin(1-7)-Mas axis Exp Physiol, May 1, 2008; 93(5): 519 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Garabelli, J. G. Modrall, J. M. Penninger, C. M. Ferrario, and M. C. Chappell Distinct roles for angiotensin-converting enzyme 2 and carboxypeptidase A in the processing of angiotensins within the murine heart Exp Physiol, May 1, 2008; 93(5): 613 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Hernandez Prada, A. J. Ferreira, M. J. Katovich, V. Shenoy, Y. Qi, R. A.S. Santos, R. K. Castellano, A. J. Lampkins, V. Gubala, D. A. Ostrov, et al. Structure-Based Identification of Small-Molecule Angiotensin-Converting Enzyme 2 Activators as Novel Antihypertensive Agents Hypertension, May 1, 2008; 51(5): 1312 - 1317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. da Costa Goncalves, R. Leite, R. A. Fraga-Silva, S. V. Pinheiro, A. B. Reis, F. M. Reis, R. M. Touyz, R. C. Webb, N. Alenina, M. Bader, et al. Evidence that the vasodilator angiotensin-(1 7)-Mas axis plays an important role in erectile function Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2588 - H2596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Chappell Emerging Evidence for a Functional Angiotensin-Converting Enzyme 2-Angiotensin-(1-7)-Mas Receptor Axis: More Than Regulation of Blood Pressure? Hypertension, October 1, 2007; 50(4): 596 - 599. [Full Text] [PDF]
|
|
|
|
|
|
A. J. Trask, D. B. Averill, D. Ganten, M. C. Chappell, and C. M. Ferrario Primary role of angiotensin-converting enzyme-2 in cardiac production of angiotensin-(1-7) in transgenic Ren-2 hypertensive rats Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3019 - H3024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Botelho-Santos, W. O. Sampaio, T. L. Reudelhuber, M. Bader, M. J. Campagnole-Santos, and R. A. Souza dos Santos Expression of an angiotensin-(1-7)-producing fusion protein in rats induced marked changes in regional vascular resistance Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2485 - H2490. [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]
|
|
|
|
|
|
W. O. Sampaio, R. A. Souza dos Santos, R. Faria-Silva, L. T. da Mata Machado, E. L. Schiffrin, and R. M. Touyz Angiotensin-(1-7) Through Receptor Mas Mediates Endothelial Nitric Oxide Synthase Activation via Akt-Dependent Pathways Hypertension, January 1, 2007; 49(1): 185 - 192. [Abstract] [Full Text] [PDF]
|
|