Zhu Guo-Qing, Patel Kuashik P, Zucker Irving H, Wang Wei
Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha, Nebraska 68198-4575, USA.
Am J Physiol Heart Circ Physiol. 2002 Jun;282(6):H2039-45. doi: 10.1152/ajpheart.00854.2001.
The aims of present study were to determine whether angiotensin II (ANG II) in the paraventricular nucleus (PVN) is involved in the central integration of the cardiac sympathetic afferent reflex and whether this effect is mediated by the ANG type 1 (AT(1)) receptor. While the animals were under alpha-chloralose and urethane anesthesia, mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) were recorded in sinoaortic-denervated and cervical-vagotomized rats. A cannula was inserted into the left PVN for microinjection of ANG II. The cardiac sympathetic afferent reflex was tested by electrical stimulation (5, 10, 20, and 30 Hz in 10 V and 1 ms) of the afferent cardiac sympathetic nerves or epicardial application of bradykinin (BK) (0.04 and 0.4 microg in 2 microl). Microinjection of ANG II (0.03, 0.3, and 3 nmol) into the PVN resulted in dose-related increases in the RSNA responses to electrical stimulation. The percent change of RSNA response to 20- and 30-Hz stimulation increased significantly at the highest dose of ANG II (3 nmol). The effects of ANG II were prevented by pretreatment with losartan (50 nmol) into the PVN. Microinjection of ANG II (0.3 nmol) into the PVN significantly enhanced the RSNA responses to epicardial application of BK, which was abolished by pretreatment with losartan (50 nmol) into the PVN. These results suggest that exogenous ANG II in the PVN augments the cardiac sympathetic afferent reflex evoked by both electrical stimulation of cardiac sympathetic afferent nerves and epicardial application of BK. These central effects of ANG II are mediated by AT(1) receptors.
本研究的目的是确定室旁核（PVN）中的血管紧张素II（ANG II）是否参与心脏交感神经传入反射的中枢整合，以及这种效应是否由1型血管紧张素（AT(1)）受体介导。在动物处于α-氯醛糖和乌拉坦麻醉状态下，记录了去窦主动脉神经和颈迷走神经切断大鼠的平均动脉压、心率和肾交感神经活动（RSNA）。将一根套管插入左PVN用于微量注射ANG II。通过电刺激（10V和1ms，频率为5、10、20和30Hz）心脏交感神经传入神经或在心外膜应用缓激肽（BK）（2μl中含0.04和0.4μg）来测试心脏交感神经传入反射。向PVN微量注射ANG II（0.03、0.3和3nmol）导致RSNA对电刺激的反应呈剂量相关增加。在ANG II最高剂量（3nmol）时，RSNA对20Hz和30Hz刺激的反应变化百分比显著增加。PVN预先注射氯沙坦（50nmol）可阻止ANG II的作用。向PVN微量注射ANG II（0.3nmol）显著增强了RSNA对心外膜应用BK的反应，而PVN预先注射氯沙坦（50nmol）可消除这种反应。这些结果表明，PVN中的外源性ANG II增强了由心脏交感神经传入神经电刺激和心外膜应用BK诱发的心脏交感神经传入反射。ANG II的这些中枢效应由AT(1)受体介导。
