Expression of an angiotensin-(1-7)-producing fusion protein in rats induced marked changes in regional vascular resistance.
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.
Botelho-Santos
Giancarla A
GA
Laboratório de Hipertensão, Dept. de Fisiologia e Biofísica, Univ. Federal de Minas Gerais, Av. Antonio Carlos, 6627-ICB, 31270-901 Belo Horizonte, MG, Brazil.
Sampaio
Walkyria O
WO
Reudelhuber
Timothy L
TL
Bader
Michael
M
Campagnole-Santos
Maria J
MJ
Souza dos Santos
Robson A
RA
D000222:Adaptation, Physiological / Q000502:physiology; D000803:Angiotensin I / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology*; D008297:Male; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013318:Stroke Volume / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology*
D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D000803:Angiotensin I; C118790:angiotensin I (1-7)