Légat Laura, Brouwers Sofie, Smolders Ilse J, Dupont Alain G
Laboratory of Pharmaceutical Chemistry, Drug Analysis and Drug Information (FASC), Research Group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), Vrije Universiteit BrusselBrussels, Belgium.
Cardiovascular Center, Universitair Ziekenhuis BrusselBrussels, Belgium.
Front Neurosci. 2017 Jun 19;11:346. doi: 10.3389/fnins.2017.00346. eCollection 2017.
Angiotensin II, glutamate and gamma-aminobutyric acid (GABA) interact within the rostral ventrolateral medulla (RVLM) and the paraventricular nucleus (PVN) modulating the central regulation of blood pressure and sympathetic tone. Our aim was to assess the effects of local angiotensin II type 2 receptor stimulation within the RVLM and the PVN on neurotransmitter concentrations and mean arterial pressure (MAP). microdialysis was used for measurement of extracellular glutamate and GABA levels and for local infusion of the angiotensin II type 2 receptor agonist Compound 21 in the RVLM and the PVN of conscious normotensive Wistar rats. The MAP response to local Compound 21 was monitored with a pressure transducer under anaesthesia. Angiotensin II type 2 receptor selectivity was assessed using the angiotensin II type 2 receptor antagonist PD123319; the GABA-A receptor antagonist bicuculline was used to assess the involvement of GABA-A receptors. Infusion of Compound 21 (0.05 μg/μl/h) in the RVLM significantly increased GABA levels and lowered blood pressure. These effects were abolished by co-infusion with PD123319. No changes in neurotransmitter levels or effects on blood pressure were seen with PD123319 infusion alone. Co-infusion of bicuculline abolished the Compound 21 evoked decrease in MAP. Infusion of Compound 21 within the PVN did not change extracellular neurotransmitter levels nor MAP. Selective stimulation of angiotensin II type 2 receptor within the RVLM by local Compound 21 infusion reduces blood pressure and increases local GABA levels in normotensive rats. This hypotensive response requires functional GABA-A receptors, suggesting that GABAergic neurons are involved in the sympatho-inhibitory action underlying this hypotensive response.
血管紧张素 II、谷氨酸和γ-氨基丁酸（GABA）在延髓头端腹外侧区（RVLM）和室旁核（PVN）内相互作用，调节血压和交感神经张力的中枢调节。我们的目的是评估RVLM和PVN内局部血管紧张素 II 2型受体刺激对神经递质浓度和平均动脉压（MAP）的影响。采用微透析法测量清醒正常血压Wistar大鼠RVLM和PVN细胞外谷氨酸和GABA水平，并局部注入血管紧张素 II 2型受体激动剂化合物21。在麻醉状态下用压力传感器监测对局部化合物21的MAP反应。使用血管紧张素 II 2型受体拮抗剂PD123319评估血管紧张素 II 2型受体选择性；使用GABA-A受体拮抗剂荷包牡丹碱评估GABA-A受体的参与情况。在RVLM中注入化合物21（0.05μg/μl/h）可显著提高GABA水平并降低血压。与PD123319共同注入可消除这些作用。单独注入PD123319时，神经递质水平无变化，对血压也无影响。共同注入荷包牡丹碱可消除化合物21引起的MAP降低。在PVN中注入化合物21不会改变细胞外神经递质水平和MAP。通过局部注入化合物21选择性刺激RVLM内的血管紧张素 II 2型受体可降低正常血压大鼠的血压并提高局部GABA水平。这种降压反应需要功能性GABA-A受体，提示GABA能神经元参与了这种降压反应潜在的交感抑制作用。
