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首页> 外文期刊>Frontiers in Neuropharmacology >Hypotensive Response to Angiotensin II Type 2 Receptor Stimulation in the Rostral Ventrolateral Medulla Requires Functional GABA-A Receptors
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Hypotensive Response to Angiotensin II Type 2 Receptor Stimulation in the Rostral Ventrolateral Medulla Requires Functional GABA-A Receptors

机译：延髓前侧延髓对血管紧张素II 2型受体刺激的低血压反应需要功能性GABA-A受体

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Objectives: Angiotensin II, glutamate and gamma-aminobutyric acid (GABA) interact within the rostral ventrolateral medulla and the paraventricular nucleus 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 rostral ventrolateral medulla and the paraventricular nucleus on neurotransmitter concentrations and mean arterial pressure. Methods: In vivo 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 rostral ventrolateral medulla and the paraventricular nucleus of conscious normotensive Wistar rats. The mean arterial pressure 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. Results: Infusion of C21 (0.05μg/μl/h) in the rostral ventrolateral medulla 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 mean arterial pressure. Infusion of Compound 21 within the paraventricular nucleus did not change extracellular neurotransmitter levels nor mean arterial pressure. Conclusion: Selective stimulation of angiotensin II type 2 receptor within the rostral ventrolateral medulla 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.
机译：目的：血管紧张素II，谷氨酸和γ-氨基丁酸（GABA）在延髓腹侧延髓和室旁核之间相互作用，调节血压和交感神经的中央调节。我们的目的是评估在延髓腹侧延髓和脑室旁核内局部血管紧张素II 2型受体刺激对神经递质浓度和平均动脉压的影响。方法：体内微透析用于测量细胞外谷氨酸和GABA水平，并在有意识的血压正常的Wistar大鼠的前额腹侧延髓和室旁核中局部注入血管紧张素II 2型受体激动剂化合物21。在麻醉下用压力传感器监测对局部化合物21的平均动脉压反应。使用血管紧张素II 2型受体拮抗剂PD123319评估了血管紧张素II 2型受体选择性。使用GABA-A受体拮抗剂bicuculline评估GABA-A受体的参与。结果：在延髓腹侧延髓中注入C21（0.05μg/μl/ h）可显着增加GABA水平并降低血压。与PD123319共同输注可消除这些影响。仅PD123319输注未见神经递质水平变化或对血压的影响。双小分子的共输注消除了化合物21引起的平均动脉压降低。在脑室旁核内输注化合物21不会改变细胞外神经递质的水平，也不会改变平均动脉压。结论：局部化合物21输注选择性刺激了延髓腹侧延髓内的血管紧张素II 2型受体降低了血压并增加了正常血压大鼠的局部GABA水平。这种降压反应需要功能性的GABA-A受体，提示GABA能神经元参与了该降压反应的交感抑制作用。

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