on March 27, 2006
Published online before print March 27, 2006, doi: 10.1161/01.HYP.0000215289.51180.5c
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Submitted on November 30, 2005
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. * To whom correspondence should be addressed. E-mail: marrob{at}ciclope.Lcc.ufmg.br.
Abstract--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.
Revised on December 24, 2005
Impairment of In Vitro and In Vivo Heart Function in Angiotensin-(1-7) Receptor Mas Knockout Mice
Robson A.S. Santos*;
Key words: receptors, angiotensin • extracellular matrix • echocardiography • heart failure • cardiac function
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