Effect of angiotensin II on voltage-gated sodium currents in aortic baroreceptor neurons and arterial baroreflex sensitivity in heart failure rats.
Effect of angiotensin II on voltage-gated sodium currents in aortic baroreceptor neurons and arterial baroreflex sensitivity in heart failure rats.
复制标题
血管紧张素 II 对心力衰竭大鼠主动脉压力感受器神经元电压门控钠电流和动脉压力反射敏感性的影响。
DOI：
10.1097/hjh.0000000000000563
复制
发表时间：
2015
影响因子：
4.9
通讯作者：
Li,Yu-Long
中科院分区：
文献类型：
--
作者：
Zhang,Dongze;Liu,Jinxu;Zheng,Hong;Tu,Huiyin;Muelleman,RobertL;Li,Yu-Long
背景：动脉压力反射敏感性的损害与慢性心力衰竭（CHF）患者的死亡率相关。血浆血管紧张素II （Ang II）升高有助于CHF患者的动脉压力反射功能障碍。主动脉压力感受器神经元中电压门控钠（Na v）通道数量的减少与chf钝化的动脉压力反射有关。方法：在本研究中，我们观察了Ang II对假手术和冠状动脉结扎诱导的CHF大鼠主动脉压力受体神经元Na - v电流和动脉压力反射的急性影响。结果：采用放射免疫法、实时逆转录pcr和western blot检测，CHF大鼠结节神经节中Angⅱ水平及血管紧张素ⅱ型1受体mRNA和蛋白表达均高于假手术大鼠。局部微注射Ang II （0.2 nmol）到结节神经节降低了假手术大鼠的动脉压力反射敏感性，而氯沙坦（1 nmol，一种血管紧张素II型1受体拮抗剂）改善了CHF大鼠的动脉压力反射敏感性。膜片钳记录数据显示，100 nmol/l的Ang II可明显抑制假手术大鼠和CHF大鼠主动脉压力感受器神经元的Na v电流。特别是，Ang II对CHF大鼠主动脉压力感受器神经元Na v电流的抑制作用大于假手术大鼠。氯沙坦（1 μmol/l）完全消除Angⅱ对假手术和CHF主动脉压力受体神经元Na v电流的抑制作用。结论：结节神经节内源性Ang II升高可能通过抑制Na - v通道导致CHF大鼠动脉压力反射功能受损。
Background:Impairment of arterial baroreflex sensitivity is associated with mortality in patients with chronic heart failure (CHF). Elevation of plasma angiotension II (Ang II) contributes to arterial baroreflex dysfunction in CHF. A reduced number of voltage-gated sodium (Na v) channels in aortic baroreceptor neurons are involved in CHF-blunted arterial baroreflex.Method:In this study, we investigated acute effect of Ang II on Na v currents in the aortic baroreceptor neuron and on arterial baroreflex in sham and coronary artery ligation-induced CHF rats.Results:Using Ang II 125 I radioimmunoassay, real-time reverse transcription-PCR and western blot, we found that Ang II levels, and mRNA and protein expression of angiotension II type 1 receptor in nodose ganglia from CHF rats were higher than that from sham rats. Local microinjection of Ang II (0.2 nmol) into the nodose ganglia decreased the arterial baroreflex sensitivity in sham rats, whereas losartan (1 nmol, an angiotension II type 1 receptor antagonist) improved the arterial baroreflex sensitivity in CHF rats. Data from patch-clamp recording showed that Ang II (100 nmol/l) acutely inhibited Na v currents in the aortic baroreceptor neurons from sham and CHF rats. In particular, inhibitory effect of Ang II on Na v currents in the aortic baroreceptor neurons was larger in CHF rats than that in sham rats. Losartan (1 μmol/l) totally abolished the inhibitory effect of Ang II on Na v currents in sham and CHF aortic baroreceptor neurons.Conclusion:These results suggest that elevation of endogenous Ang II in the nodose ganglia contributes to impairment of the arterial baroreflex function in CHF rats through inhibiting Na v channels.