Submitted on November 14, 2006
Accepted on January 4, 2007
EXPRESSION OF AN ANGIOTENSIN-(1-7)-PRODUCING FUSION PROTEIN IN RATS INDUCED MARKED CHANGES IN REGIONAL VASCULAR RESISTANCE
Giancarla Aparecida Botelho-Santos1, Walkyria Oliveira Sampaio2, Timothy L. Reudelhuber3, Michael Bader4, Maria J Campagnole-Santos5, and Robson A Santos6*
1 Physiology and Byophysics, Federal University of Minas Gerais, Belo Horizonte , Minas Gerais, Brazil
2 Physiology and Byophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
3 Biochemical Laboratory, Clinical Research Institute of Montreal, Montreal, Canada
4 Max Delbruck-Center for Molecular Medicine, Institut für Informatik, Garching, Germany
5 Physiology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
6 Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
* To whom correspondence should be addressed. E-mail: robsonsant{at}gmail.com.
We have described a transgenic rat line which express 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 TG rats had similar level of baseline blood pressure (99 ± 3 mmHg) as SD rats (101 ± 3 mmHg). However, pronounced differences were observed in other hemodynamic measurements. TGR(A1-7)3292 rats presented a significantly increase in stroke volume (0.29 ± 0.01 ml vs 0.25 ± 0.01 ml in SD), increased cardiac index (24.6 ± 0.91 ml/ min.Kg vs 21.9 ± 0.65 ml/ min.Kg) and decreased total peripheral resistance (3.9 ± 0.13 mmHg.ml -1 .min.100g vs 4.5 ± 0.13 mmHg.ml -1 .min.100g). The increase in stroke volume in TGR may be partially explained by the small decrease in HR (326 ± 7.0 beats/ min 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.
