Expression of an angiotensin-(1-7)-producing fusion protein in rats induced marked changes in regional vascular resistance
Expression of an angiotensin-(1-7)-producing fusion protein in rats induced marked changes in regional vascular resistance
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DOI：
10.1152/ajpheart.01245.2006
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发表时间：
2007-05-01
影响因子：
4.8
通讯作者：
dos Santos, Robson A. Souza
中科院分区：
文献类型：
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作者：
Botelho-Santos, Giancarla A.;Sampaio, Walkyria O.;dos Santos, Robson A. Souza
我们描述了一种转基因大鼠系，表达一种产生血管紧张素（1-7）的融合蛋白TGR(A1-7)3292。在这些大鼠中，睾丸充当血管紧张素-(1-7)生物泵，使其血浆浓度增加2.5倍。在这项研究中，我们使用荧光微球对TGR(A1-7)3292和年龄匹配的汉诺威斯普拉格-道利（SD）对照大鼠进行了血流动力学测量。经脲麻醉的转基因大鼠的基线血压水平（99 +/- 3mmhg）与SD大鼠（101 +/- 3mmhg）相似。然而，在其他血流动力学测量中观察到明显的差异。TGR(A1-7)3292大鼠脑卒中容量显著增加（SD为0.29 +/- 0.01 ml比0.25 +/- 0.01 ml），心脏指数增加（24.6 +/- 0.91比21.9 +/- 0.65 ml中心dot min（-1）中心dot kg），总外周阻力降低（3.9 +/- 0.13比4.5 +/- 0.13 mmHg中心dot ml（-1）中心dot min中心dot 100 g）。转基因大鼠脑卒中量增加的部分原因可能是其心率的小幅下降（SD值为326 +/- 7.0 vs. 359 +/- 6.0）。TGR(A1-7)3292大鼠肺、脾、肾、肾上腺、脑、睾丸和棕色脂肪组织的血管阻力明显降低，而左心室、肠系膜、皮肤、腓肠肌和白色脂肪组织的血管阻力无显著差异。这些结果证实并扩展了先前急性血管紧张素-(1-7)输注后观察到的结果，表明循环血管紧张素（1-7）的慢性增加会对局部和全身血流动力学产生持续和重要的变化。此外，我们的数据表明血管紧张素-(1-7)在局部血流的强直控制中的生理作用。
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 center dot min(-1)center dot kg) and decreased total peripheral resistance (3.9 +/- 0.13 vs. 4.5 +/- 0.13 mmHg center dot ml(-1)center dot min center dot 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.