Ma R, Schultz H D, Wang W
Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha, Nebraska 68198-4575, USA.
Am J Physiol. 1999 Jul;277(1):H15-22. doi: 10.1152/ajpheart.1999.277.1.H15.
The aims of this study were to determine whether ANG II is involved in the central integration of the cardiac sympathetic afferent reflex (CSAR), and if this central effect of ANG II is mediated by the AT(1) receptor. Experiments were undertaken in dogs that were anesthetized with alpha-chloralose, sinoaortic denervated, and vagotomized. The renal sympathetic nerve activity (RSNA) responses to varying frequency and voltage stimulation of cardiac sympathetic afferent nerves were used to evaluate the central sensitivity of the CSAR. In two groups of dogs, two doses (50 and 100 ng/min icv) of ANG II were acutely infused. In a third group of dogs, ANG II was chronically infused for 3 days (100 ng/min, 1 microliter/h icv). We found that acute infusion into the cerebroventricle of two doses of ANG II did not affect the central sensitivity of the CSAR or the baseline hemodynamics, but the baseline RSNA increased significantly during the infusion of the higher dose of ANG II. However, chronic intracerebroventricular infusion of ANG II enhanced the central sensitivity of the CSAR significantly. In addition, chronic intracerebrovetricular infusion of ANG II elicited a significant increase in water intake and in arterial pressure from the first and second day of infusion, respectively. In the group that received chronic intracerebroventricular infusion of ANG II, the administration of an AT(1)-receptor antagonist losartan (0.125 mg/kg icv) abolished ANG II-induced augmentation of the CSAR. These results suggest that chronic elevation of central ANG II can sensitize the CSAR via central AT(1) receptors.
本研究的目的是确定血管紧张素II（ANG II）是否参与心脏交感神经传入反射（CSAR）的中枢整合，以及ANG II的这种中枢效应是否由AT(1)受体介导。实验在使用α-氯醛糖麻醉、去窦主动脉神经和切断迷走神经的犬身上进行。通过肾交感神经活动（RSNA）对心脏交感神经传入神经不同频率和电压刺激的反应来评估CSAR的中枢敏感性。在两组犬中，急性输注两种剂量（50和100 ng/min脑室内注射）的ANG II。在第三组犬中，ANG II持续输注3天（100 ng/min，1微升/小时脑室内注射）。我们发现，向脑室急性输注两种剂量的ANG II不影响CSAR的中枢敏感性或基线血流动力学，但在输注较高剂量的ANG II期间，基线RSNA显著增加。然而，ANG II的慢性脑室内输注显著增强了CSAR的中枢敏感性。此外，ANG II的慢性脑室内输注分别在输注的第一天和第二天引起饮水量和动脉压显著增加。在接受ANG II慢性脑室内输注的组中，给予AT(1)受体拮抗剂氯沙坦（0.125 mg/kg脑室内注射）可消除ANG II诱导的CSAR增强。这些结果表明，中枢ANG II的慢性升高可通过中枢AT(1)受体使CSAR敏感化。
