Department of Emergency Medicine, Univ. of Nebraska Medical Center, Omaha, NE 68198-1150, USA.
Am J Physiol Cell Physiol. 2010 Jan;298(1):C98-C106. doi: 10.1152/ajpcell.00321.2009. Epub 2009 Oct 21.
As an endogenous physiologically active peptide, angiotensin (ANG) II plays an important role in the maintenance of blood pressure. In the arterial baroreceptor reflex (a pivotal regulator of blood pressure), aortic baroreceptor (AB) neurons located in the nodose ganglia (NG) are a primary afferent limb of the baroreflex. Hyperpolarization-activated currents (I(h)) in the AB neurons contribute to the excitability of the AB neurons. Therefore, the present study was to measure the modulating effect of ANG II on the I(h) in the primary AB neurons isolated from rats. Data from immunofluorescent and Western blot analyses showed that protein of AT(1) and AT(2) receptors was expressed in the nodose neurons. In the whole cell patch-clamp recording, ANG II concentration dependently enhanced the I(h) density in the AB neurons (100 nM ANG II-induced 53.8 +/- 3.8% increase for A-type AB neurons and 30.4 +/- 7.7% increase for C-type AB neurons at test pulse -140 mV, P < 0.05). ANG II also decreased membrane excitability in the AB neurons. AT(1) receptor antagonist (1 muM losartan) but not AT(2) receptor antagonist (1 muM PD-123,319) totally abolished the effect of ANG II on the I(h) and neuronal excitability. In addition, NADPH oxidase inhibitor (100 muM apocynin) and superoxide scavenger (1 mM tempol) also significantly blunted the ANG II-induced increase of the I(h) and decrease of the membrane excitability in the AB neurons. Furthermore, losartan, apocynin, or tempol significantly attenuated the superoxide overproduction in the NG tissues induced by ANG II. These results suggest that ANG II-NADPH oxidase-superoxide signaling can activate the I(h) and subsequently decrease the membrane excitability of rat AB neurons.
作为一种内源性生理活性肽，血管紧张素（ANG）II 在维持血压方面发挥着重要作用。在动脉压力感受器反射（血压的关键调节机制）中，位于结状神经节（NG）中的主动脉压力感受器（AB）神经元是压力反射的主要传入神经。AB 神经元中的超极化激活电流（I(h)）有助于 AB 神经元的兴奋性。因此，本研究旨在测量 ANG II 对从大鼠分离的原代 AB 神经元中 I(h)的调节作用。免疫荧光和 Western blot 分析数据显示，AT(1)和 AT(2)受体蛋白在结状神经元中表达。在全细胞膜片钳记录中，ANG II 浓度依赖性地增强了 AB 神经元中的 I(h)密度（100 nM ANG II 诱导 A 型 AB 神经元的 53.8 +/- 3.8%增加，C 型 AB 神经元的 30.4 +/- 7.7%增加，测试脉冲为-140 mV，P < 0.05）。ANG II 还降低了 AB 神经元的膜兴奋性。AT(1)受体拮抗剂（1 μM 洛沙坦）但不是 AT(2)受体拮抗剂（1 μM PD-123,319）完全消除了 ANG II 对 I(h)和神经元兴奋性的影响。此外，NADPH 氧化酶抑制剂（100 μM 阿朴肉桂酸）和超氧化物清除剂（1 mM 替米泊芬）也显著减弱了 ANG II 诱导的 I(h)增加和 AB 神经元膜兴奋性降低。此外，洛沙坦、阿朴肉桂酸或替米泊芬显著减轻了 ANG II 诱导的 NG 组织中超氧化物的过度产生。这些结果表明，ANG II-NADPH 氧化酶-超氧化物信号可以激活 I(h)，随后降低大鼠 AB 神经元的膜兴奋性。
