McMullan Simon, Goodchild Ann K, Pilowsky Paul M
Hypertension and Stroke Research Laboratory, University of Sydney, NSW, Australia.
J Physiol. 2007 Jul 15;582(Pt 2):711-22. doi: 10.1113/jphysiol.2007.128983. Epub 2007 Mar 15.
Chronic intravenous angiotensin II (Ang II) has been widely used to establish centrally mediated hypertension in experimental animals, and disruption of Ang II activity is a frontline treatment for hypertensive disease. However, the acute central actions of circulating Ang II are poorly understood. We examined the effects of intravenous pressor doses of Ang II on autonomic activity in anaesthetized rats under neuromuscular blockade, and compared baroinhibition evoked by Ang II pressor ramps to equipressor responses evoked by phenylephrine (PE). Baroinhibition of splanchnic sympathetic nerve activity was attenuated during Ang II trials compared with PE, and rats remained sensitive to electrical stimulation of the aortic depressor nerve at higher arterial pressures during Ang II trials. This was not due to a direct effect of Ang II on aortic nerve baroreceptors. In a separate series of experiments, we provide direct evidence that bulbospinal barosensitive neurones in the rostral ventrolateral medulla are differentially sensitive to pressure ramps evoked by Ang II or PE vasoconstriction. Nineteen out of 41 units were equally sensitive to increased arterial pressure evoked by Ang II or PE. In 17 of 41 units, barosensitivity was attenuated during Ang II trials, and in five of 41 cases units that had previously been barosensitive increased their firing rate during Ang II trials. These results show, for the first time, that circulating Ang II acutely modulates central cardiovascular control mechanisms. We suggest that this results from activation by Ang II of a central pathway originating at the circumventricular organs.
慢性静脉注射血管紧张素II（Ang II）已被广泛用于在实验动物中建立中枢介导的高血压，而破坏Ang II活性是高血压疾病的一线治疗方法。然而，循环Ang II的急性中枢作用却知之甚少。我们研究了静脉注射升压剂量的Ang II对神经肌肉阻滞下麻醉大鼠自主神经活动的影响，并将Ang II升压斜坡诱发的压力抑制与去氧肾上腺素（PE）诱发的等压反应进行比较。与PE相比，在Ang II试验期间，内脏交感神经活动的压力抑制减弱，并且在Ang II试验期间，大鼠在较高动脉压下对主动脉减压神经的电刺激仍保持敏感。这并非由于Ang II对主动脉神经压力感受器的直接作用。在另一系列实验中，我们提供了直接证据，即延髓头端腹外侧的延髓脊髓压力敏感神经元对Ang II或PE血管收缩诱发的压力斜坡具有不同的敏感性。41个单位中有19个对Ang II或PE诱发的动脉压升高同样敏感。在41个单位中的17个中，在Ang II试验期间压力敏感性减弱，在41个案例中的5个中，先前具有压力敏感性的单位在Ang II试验期间其放电频率增加。这些结果首次表明，循环Ang II可急性调节中枢心血管控制机制。我们认为，这是由于Ang II激活了起源于室周器官的中枢途径所致。
