Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan; and.
Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan; and Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Am J Physiol Heart Circ Physiol. 2014 Sep 1;307(5):H701-9. doi: 10.1152/ajpheart.00005.2014. Epub 2014 Jul 3.
The central nervous system plays an important role in regulating sympathetic outflow and arterial pressure in response to ethanol exposure. However, the underlying neural mechanisms have not been fully understood. In the present study, we tested the hypothesis that injection of ethanol in the central nucleus of the amygdala (CeA) increases sympathetic outflow, which may require the activation of local ionotropic excitatory amino acid receptors. In anesthetized rats, CeA injection of ethanol (0, 0.17, and 1.7 μmol) increased splanchnic sympathetic nerve activity (SSNA), lumbar sympathetic nerve activity (LSNA), and mean arterial pressure (MAP) in a dose-dependent manner. A cocktail containing ethanol (1.7 μmol) and kynurenate (KYN), an ionotropic excitatory amino acid receptor blocker, showed significantly blunted sympathoexcitatory and pressor responses compared with those elicited by CeA-injected ethanol alone (P < 0.01). A cocktail containing ethanol and d-2-amino-5-phosphonovalerate, an N-methyl-d-aspartate (NMDA) receptor antagonist, elicited attenuated sympathoexcitatory and pressor responses that were significantly less than ethanol alone (P < 0.01). In addition, CeA injection of acetate (0.20 μmol, n = 7), an ethanol metabolite, consistently elicited sympathoexcitatory and pressor responses, which were effectively blocked by d-2-amino-5-phosphonovalerate (n = 9, P < 0.05). Inhibition of neuronal activity of the rostral ventrolateral medulla (RVLM) with KYN significantly (P < 0.01) attenuated sympathoexcitatory responses elicited by CeA-injected ethanol. Double labeling of immune fluorescence showed NMDA NR1 receptor expression in CeA neurons projecting to the RVLM. We conclude that ethanol and acetate increase sympathetic outflow and arterial pressure, which may involve the activation of NMDA receptors in CeA neurons projecting to the RVLM.
中枢神经系统在调节交感神经输出和动脉血压以响应乙醇暴露方面发挥重要作用。然而，其潜在的神经机制尚未完全理解。在本研究中，我们检验了这样一个假设，即向杏仁中央核（CeA）内注射乙醇会增加交感神经输出，这可能需要局部离子型兴奋性氨基酸受体的激活。在麻醉大鼠中，CeA 内注射乙醇（0、0.17 和 1.7μmol）以剂量依赖性方式增加内脏交感神经活动（SSNA）、腰交感神经活动（LSNA）和平均动脉压（MAP）。包含乙醇（1.7μmol）和犬尿酸（KYN）的混合物（一种离子型兴奋性氨基酸受体阻滞剂）显示出与单独注射 CeA 乙醇引起的交感兴奋和升压反应明显减弱（P<0.01）。包含乙醇和 d-2-氨基-5-膦戊酸（NMDA 受体拮抗剂）的混合物引起的交感兴奋和升压反应减弱，明显小于单独注射乙醇（P<0.01）。此外，CeA 内注射乙醇代谢物醋酸盐（0.20μmol，n=7）始终引起交感兴奋和升压反应，这些反应被 d-2-氨基-5-膦戊酸有效阻断（n=9，P<0.05）。KYN 抑制延髓头端腹外侧区（RVLM）神经元活动显著（P<0.01）减弱了 CeA 内注射乙醇引起的交感兴奋反应。免疫荧光双重标记显示 NMDA NR1 受体在投射到 RVLM 的 CeA 神经元中表达。我们得出结论，乙醇和醋酸盐增加交感神经输出和动脉血压，这可能涉及投射到 RVLM 的 CeA 神经元中 NMDA 受体的激活。
