Diz Debra I, Garcia-Espinosa Maria A, Gegick Stephen, Tommasi Ellen N, Ferrario Carlos M, Ann Tallant E, Chappell Mark C, Gallagher Patricia E
The Hypertension & Vascular Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1032, USA.
Exp Physiol. 2008 May;93(5):694-700. doi: 10.1113/expphysiol.2007.040261. Epub 2008 Mar 20.
Injections of the angiotensin(1-7) [Ang(1-7)] antagonist [d-Ala7]-Ang(1-7) into the nucleus of the solitary tract (NTS) of Sprague-Dawley rats reduce baroreceptor reflex sensitivity (BRS) for control of heart rate by approximately 40%, whereas injections of the angiotensin II (Ang II) type 1 receptor antagonist candesartan increase BRS by 40% when reflex bradycardia is assessed. The enzyme angiotensin-converting enzyme 2 (ACE2) is known to convert Ang II to Ang(1-7). We report that ACE2 activity, as well as ACE and neprilysin activities, are present in plasma membrane fractions of the dorsomedial medulla of Sprague-Dawley rats. Moreover, we show that BRS for reflex bradycardia is attenuated (1.16 +/- 0.29 ms mmHg-1 before versus 0.33 +/- 0.11 ms mmHg-1 after; P < 0.05; n = 8) 30-60 min following injection of the selective ACE2 inhibitor MLN4760 (12 pmol in 120 nl) into the NTS. These findings support the concept that within the NTS, local synthesis of Ang(1-7) from Ang II is required for normal sensitivity for the baroreflex control of heart rate in response to increases in arterial pressure.
向Sprague-Dawley大鼠的孤束核（NTS）注射血管紧张素（1-7）[Ang(1-7)]拮抗剂[d-Ala7]-Ang(1-7)，可使控制心率的压力感受器反射敏感性（BRS）降低约40%，而在评估反射性心动过缓时，注射血管紧张素II（Ang II）1型受体拮抗剂坎地沙坦可使BRS增加40%。已知血管紧张素转换酶2（ACE2）可将Ang II转化为Ang(1-7)。我们报告，在Sprague-Dawley大鼠延髓背内侧的质膜部分存在ACE2活性，以及ACE和中性内肽酶活性。此外，我们发现，在向NTS注射选择性ACE2抑制剂MLN4760（120 nl中含12皮摩尔）后30 - 60分钟，反射性心动过缓的BRS减弱（注射前为1.16±0.29毫秒/毫米汞柱，注射后为0.33±0.11毫秒/毫米汞柱；P<0.05；n = 8）。这些发现支持了这样一种观点，即在NTS内，从Ang II局部合成Ang(1-7)是对动脉压升高做出心率压力反射控制正常敏感性所必需的。
