Impairment of in vitro and in vivo heart function in angiotensin-(1-7) receptor Mas knockout mice

Item Type:	Article
Title:	Impairment of in vitro and in vivo heart function in angiotensin-(1-7) receptor Mas knockout mice
Creators Name:	Santos, R.A. and Castro, C.H. and Gava, E. and Pinheiro, S.V. and Almeida, A.P. and de Paula, R.D. and Cruz, J.S. and Ramos, A.S. and Rosa, K.T. and Irigoyen, M.C. and Bader, M. and Alenina, N. and Kitten, G.T. and Ferreira, A.J.
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.
Keywords:	Angiotensin I, Calcium Channels, Cardiac Myocytes, Collagen, Coronary Vessels, Echocardiography, Electrophysiology, Heart, Heart Rate, Knockout Mice, Myocardial Contraction, Myocardium, Peptide Fragments, Proto-Oncogene Proteins, G-Protein-Coupled Receptors, Systole, Vascular Resistance, Ventricular Function, Animals, Mice
Source:	Hypertension
ISSN:	0194-911X
Publisher:	American Heart Association
Volume:	547
Number:	5
Page Range:	996-1002
Date:	May 2006
Official Publication:	https://doi.org/10.1161/01.HYP.0000215289.51180.5c
PubMed:	View item in PubMed

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