on September 12, 2005
Published online before print September 12, 2005, doi: 10.1161/01.HYP.0000175813.04375.8a
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on April 23, 2005
From the Departments of Physiology and Biophysics (C.H.C., R.A.S.d.S., A.P.d.A.) and Morphology (A.J.F.), Federal University of Minas Gerais, Belo Horizonte, Brazil, and the Max Delbrück Center for Molecular Medicine (M.B., N.A.), Berlin-Buch, Germany. * To whom correspondence should be addressed. E-mail: apa{at}icb.ufmg.br.
Abstract--The aim of this study was to evaluate the angiotensin (Ang)-(1-7) effects in isolated mouse hearts. The hearts of male C57BL/6J and knockout mice for the Ang-(1-7) receptor Mas were perfused by the Langendorff method. After a basal period, the hearts were perfused for 20 minutes with Krebs-Ringer solution (KRS) alone (control) or KRS containing Ang-(1-7) (0.22 pmol/L), the Mas antagonist A-779 (115 nmol/L), the angiotensin type 1 receptor antagonist losartan (2.2 µmol/L), or the angiotensin type 2 receptor antagonist PD123319 (130 nmol/L). To evaluate the involvement of Ang receptors, prostaglandins, and nitric oxide in the Ang-(1-7) effects, the hearts were perfused for 20 to 30 minutes with KRS containing either A-779, losartan, PD123319, indomethacin, or NG-nitro-L-arginine methyl ester (L-NAME) alone or in association with subsequent Ang-(1-7) perfusion. In addition, hearts from Mas-knockout mice were perfused for 20 minutes with KRS containing Ang-(1-7) (0.22 pmol/L) and losartan. Ang-(1-7) alone did not change the perfusion pressure. Strikingly, in the presence of losartan, 0.22 pmol/L Ang-(1-7) induced a significant decrease in perfusion pressure, which was blocked by A-779, indomethacin, and L-NAME. Furthermore, this effect was not observed in Mas-knockout mice. In contrast, in the presence of PD123319, Ang-(1-7) produced a significant increase in perfusion pressure. This change was not modified by the addition of A-779. Losartan reduced but did not abolish this effect. Our results suggest that Ang-(1-7) produces complex vascular effects in isolated, perfused mouse hearts involving interaction of its receptor with angiotensin type 1- and type 2-related mechanisms, leading to the release of prostaglandins and nitric oxide.
Revised on May 17, 2005
Evidence for a Functional Interaction of the Angiotensin-(1-7) Receptor Mas With AT1 and AT2 Receptors in the Mouse Heart
Carlos Henrique de Castro;
Key words: receptors, angiotensin • cardiac function • heart • angiotensin antagonist • prostaglandins
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
P. Xu, A. C. Costa-Goncalves, M. Todiras, L. A. Rabelo, W. O. Sampaio, M. M. Moura, S. Sousa Santos, F. C. Luft, M. Bader, V. Gross, et al. Endothelial Dysfunction and Elevated Blood Pressure in Mas Gene-Deleted Mice Hypertension, February 1, 2008; 51(2): 574 - 580. [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]
|
|
|
|
 |
|
 L. K. Becker, G. M. Etelvino, T. Walther, R. A. S. Santos, and M. J. Campagnole-Santos Immunofluorescence localization of the receptor Mas in cardiovascular-related areas of the rat brain Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1416 - H1424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C De Mello, C. M Ferrario, and J. A Jessup Beneficial versus harmful effects of Angiotensin (1-7) on impulse propagation and cardiac arrhythmias in the failing heart Journal of Renin-Angiotensin-Aldosterone System, June 1, 2007; 8(2): 74 - 80. [Abstract] [PDF]
|
|
|
|
 |
|
 N. Toda, K. Ayajiki, and T. Okamura Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation Pharmacol. Rev., March 1, 2007; 59(1): 54 - 87. [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]
|
|
|
|
 |
|
 M. Canals, L. Jenkins, E. Kellett, and G. Milligan Up-regulation of the Angiotensin II Type 1 Receptor by the MAS Proto-oncogene Is Due to Constitutive Activation of Gq/G11 by MAS J. Biol. Chem., June 16, 2006; 281(24): 16757 - 16767. [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]
|
|
|
|
|
|
R. A.S. Santos, C. H. Castro, E. Gava, S. V.B. Pinheiro, A. P. Almeida, R. D. de Paula, J. S. Cruz, A. S. Ramos, K. T. Rosa, M. C. Irigoyen, et al. Impairment of In Vitro and In Vivo Heart Function in Angiotensin-(1-7) Receptor Mas Knockout Mice Hypertension, May 1, 2006; 47(5): 996 - 1002. [Abstract] [Full Text] [PDF]
|
|