Couto Aurea S, Baltatu Ovidiu, Santos Robson A S, Ganten Detlev, Bader Michael, Campagnole-Santos Maria J
Departamento de Fisiologia e Biofísica, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
J Hypertens. 2002 May;20(5):919-25. doi: 10.1097/00004872-200205000-00027.
In this study, we investigated the effects of angiotensin II and angiotensin-(1-7) at the nucleus tractus solitarii (nTS) in transgenic rats with a severe deficit in brain angiotensinogen production, TGR(ASrAOGEN) (TGR).
Angiotensin II (10 pmol), angiotensin-(1-7) (10 pmol) or NaCl (0.9%/50 nl) were microinjected into the nTS of urethane-anaesthetized TGR (n = 36) and Sprague Dawley (SD) (n = 34) rats. Mean arterial pressure (MAP) and heart rate were measured via a femoral artery catheter and the baroreflex control of heart rate was evaluated after increases in MAP induced by phenylephrine (baroreflex bradycardia).
Angiotensin II microinjections into the nTS of the TGR induced a higher decrease in MAP and heart rate (-37 +/- 5 mmHg and -69 +/- 12 b.p.m., respectively) in comparison to SD rats (-18 +/- 1 mmHg and -43 +/- 5 b.p.m., respectively). In contrast, changes after angiotensin-(1-7) microinjections into the nTS of TGR (-6 +/- 1 mmHg and -13 +/- 4 b.p.m.) were significantly smaller than that induced in SD (-11 +/- 2 mmHg and -24 +/- 6 b.p.m.). The baseline baroreflex sensitivity to phenylephrine of TGR was accentuated in comparison to SD rats (0.70 +/- 0.06 versus 0.44 +/- 0.03 ms/mmHg). Angiotensin II microinjection into the nTS produced similar attenuation in the baroreflex bradycardia in both SD (0.28 +/- 0.07 versus 0.5 +/- 0.07 ms/mmHg, before injection) and TGR (0.44 +/- 0.1 versus 0.82 +/- 0.1 ms/mmHg, before injection). In contrast, angiotensin-(1-7) microinjection elicited a facilitation of the baroreflex bradycardia in SD (0.68 +/- 0.12 versus 0.41 +/- 0.03 ms/mmHg, before injection), while in TGR, angiotensin-(1-7) induced an attenuation of baroreflex bradycardia (0.34 +/- 0.07 ms/mmHg versus 0.55 +/- 0.05 ms/mmHg, before injection).
These results indicate that a permanent inhibition of angiotensinogen synthesis in the brain can lead to an increase in the sensitivity of the baroreflex control of heart rate (baroreflex bradycardia) and an increase in angiotensin II responsiveness at the nTS. However, the nTS effect of angiotensin-(1-7) was significantly attenuated in these transgenic rats. These data further indicate that the decrease in brain angiotensins in the transgenic rats may be functionally relevant and support the concept of differential regulatory mechanisms for the effects of the two angiotensin peptides.
在本研究中，我们研究了血管紧张素II和血管紧张素 -（1 - 7）对脑内血管紧张素原严重缺乏的转基因大鼠孤束核（nTS）的影响，即TGR（ASrAOGEN）（TGR）大鼠。
将血管紧张素II（10 pmol）、血管紧张素 -（1 - 7）（10 pmol）或氯化钠（0.9%/50 nl）微量注射到经乌拉坦麻醉的TGR大鼠（n = 36）和Sprague Dawley（SD）大鼠（n = 34）的nTS中。通过股动脉导管测量平均动脉压（MAP）和心率，并在去氧肾上腺素诱导MAP升高后评估心率的压力反射控制（压力反射性心动过缓）。
与SD大鼠相比，向TGR大鼠的nTS中微量注射血管紧张素II导致MAP和心率下降幅度更大（分别为-37±5 mmHg和-69±12次/分钟），而SD大鼠分别为-18±1 mmHg和-43±5次/分钟。相反，向TGR大鼠的nTS中微量注射血管紧张素 -（1 - 7）后的变化（-6±1 mmHg和-13±4次/分钟）明显小于SD大鼠（-11±2 mmHg和-24±6次/分钟）。与SD大鼠相比，TGR大鼠对去氧肾上腺素的基线压力反射敏感性增强（0.70±0.06对0.44±0.03 ms/mmHg）。向nTS中微量注射血管紧张素II在SD大鼠（注射前为0.5±0.07对0.28±0.07 ms/mmHg）和TGR大鼠（注射前为0.82±0.1对0.44±0.1 ms/mmHg）中对压力反射性心动过缓产生了类似的减弱作用。相反，向SD大鼠的nTS中微量注射血管紧张素 -（1 - 7）促进了压力反射性心动过缓（注射前为0.41±0.03对0.68±0.12 ms/mmHg），而在TGR大鼠中，血管紧张素 -（1 - 7）则导致压力反射性心动过缓减弱（注射前为0.55±0.05对0.34±0.07 ms/mmHg）。
这些结果表明，脑内血管紧张素原合成的永久性抑制可导致心率压力反射控制（压力反射性心动过缓）敏感性增加以及nTS对血管紧张素II反应性增加。然而，在这些转基因大鼠中，血管紧张素 -（1 - 7）的nTS效应明显减弱。这些数据进一步表明，转基因大鼠脑内血管紧张素的减少可能在功能上具有相关性，并支持两种血管紧张素肽作用的差异调节机制的概念。
