AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 292: H2485-H2490, 2007. First published January 5, 2007; doi:10.1152/ajpheart.01245.2006
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Expression of an angiotensin-(1-7)-producing fusion protein in rats induced marked changes in regional vascular resistance

Giancarla A. Botelho-Santos,1 Walkyria O. Sampaio,1 Timothy L. Reudelhuber,2 Michael Bader,3 Maria J. Campagnole-Santos,1 and Robson A. Souza dos Santos1

1Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil; 2Canadian Institutes for Health Research Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec, Canada; and 3Max Delbruck Center for Molecular Medicine, Berlin-Buch, Germany

Submitted 14 November 2006 ; accepted in final form 4 January 2007

We have described a transgenic rat line that expresses an angiotensin-(1-7)-producing fusion protein, the TGR(A1-7)3292. In these rats, testis acts as an angiotensin-(1-7) biological pump, increasing its plasma concentration 2.5-fold. In this study, we performed hemodynamic measurements in TGR(A1-7)3292 and age-matched Hannover Sprague-Dawley (SD) control rats, using fluorescent microspheres. Urethane-anesthetized transgenic rats had similar levels of baseline blood pressure (99 ± 3 mmHg) as did SD rats (101 ± 3 mmHg). However, pronounced differences were observed in other hemodynamic measurements. TGR(A1-7)3292 rats presented a significant increase in stroke volume (0.29 ± 0.01 vs. 0.25 ± 0.01 ml in SD), increased cardiac index (24.6 ± 0.91 vs. 21.9 ± 0.65 ml·min–1·kg) and decreased total peripheral resistance (3.9 ± 0.13 vs. 4.5 ± 0.13 mmHg·ml–1·min·100 g). The increase in stroke volume in transgenic rats may be partially explained by the small decrease in heart rate (326 ± 7.0 vs. 359 ± 6.0 beats/min in SD). Strikingly, TGR(A1-7)3292 rats presented a substantial decrease in the vascular resistance in lung, spleen, kidney, adrenals, brain, testis and brown fat tissue with no significant differences in the left ventricle, mesentery, skin, gastrocnemius muscle and white fat tissue. These results corroborate and extend previous results observed after acute angiotensin-(1-7) infusion, showing that chronic increase in circulating angiotensin-(1-7) produces sustained and important changes in regional and systemic hemodynamics. Moreover, our data suggest a physiological role for angiotensin-(1-7) in the tonic control of regional blood flow.

hemodynamic; blood flow; fluorescent microspheres; transgenic rats


Address for reprint requests and other correspondence: R. A. S. Santos, Laboratório de Hipertensão, Dept. de Fisiologia e Biofísica, Univ. Federal de Minas Gerais, Av. Antonio Carlos, 6627-ICB, 31270-901, Belo Horizonte, MG, Brazil (e-mail: robsonsant{at}gmail.com)




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