Paton Julian F R, Wang Sheng, Polson Jaimie W, Kasparov Sergey
Department of Physiology & Pharmacology, Bristol Heart Institute, School of Medical Sciences, University of Bristol, Bristol, UK.
J Mol Med (Berl). 2008 Jun;86(6):705-10. doi: 10.1007/s00109-008-0324-4. Epub 2008 Apr 29.
Angiotensin II (AngII) is a major culprit in essential hypertension. Based on a genetic rodent model of hypertension, we review here evidence that AngII may signal across the blood brain barrier to affect neuronal circuits within the nucleus tractus solitarii (NTS) of the brainstem, a pivotal region regulating both the baroreceptor reflex and set point control of arterial pressure. We have termed this form of signalling as vascular-neuronal signalling. We describe that the depressant action of AngII in NTS on the baroreceptor reflex is mediated via activation of endothelial nitric oxide synthase (eNOS) releasing NO that promotes release of the inhibitory transmitter-GABA. This could shunt the incoming excitatory baroreceptor afferent traffic impinging on NTS neurones. Chronic studies recording arterial pressure in conscious unrestrained rats using radio-telemetry have revealed that eNOS in NTS plays an endogenous physiological role in the homeostatic regulation of the gain of the cardiac baroreceptor reflex. However, in the spontaneously hypertensive rat, eNOS mRNA was higher (compared to normotensive rats), and its chronic blockade in NTS restored the abnormally depressed cardiac baroreceptor reflex to levels akin to normotensive rats, improved heart rate variability and lowered arterial pressure. Hence, it seems that excessive eNOS activity in NTS of the SHR contributes to the pathological state of this animal model's cardiovascular autonomic nervous system. We speculate on why eNOS activity may be up regulated in the NTS of the SHR and propose that it is a consequence of high cerebral vascular resistance and inadequate blood perfusion of the brainstem.
血管紧张素 II（AngII）是原发性高血压的主要致病因素。基于高血压的遗传性啮齿动物模型，我们在此回顾相关证据，即 AngII 可能通过血脑屏障发出信号，影响脑干孤束核（NTS）内的神经回路，NTS 是调节压力感受器反射和动脉血压设定点控制的关键区域。我们将这种信号传导形式称为血管 - 神经元信号传导。我们描述了 AngII 在 NTS 中对压力感受器反射的抑制作用是通过激活内皮型一氧化氮合酶（eNOS）释放 NO 来介导的，NO 促进抑制性神经递质 - GABA 的释放。这可能会分流传入 NTS 神经元的兴奋性压力感受器传入信号。使用无线电遥测技术对清醒不受约束大鼠的动脉血压进行的长期研究表明，NTS 中的 eNOS 在心脏压力感受器反射增益的稳态调节中发挥内源性生理作用。然而，在自发性高血压大鼠中，eNOS mRNA 水平更高（与正常血压大鼠相比），并且在 NTS 中对其进行长期阻断可将异常降低的心脏压力感受器反射恢复到与正常血压大鼠相似的水平，改善心率变异性并降低动脉血压。因此，似乎 SHR 的 NTS 中 eNOS 活性过高促成了该动物模型心血管自主神经系统的病理状态。我们推测为什么 SHR 的 NTS 中 eNOS 活性可能上调，并提出这是脑血管阻力高和脑干血液灌注不足的结果。
