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Angiotensin-II-mediated AT1 receptor stimulation increases glutamate release within the rostral ventrolateral medulla of normotensive rats

Hypertension Research volume 43, pages 848–850 (2020)Cite this article

Zhou et al. [1] recently reported in Hypertension Research that N-methyl-D-aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor expression and glutamate concentrations in the rostral ventrolateral medulla (RVLM) were increased in a rat model of stress-induced hypertension (SIH). Chronic intracerebroventricular (ICV) perfusion of the angiotensin II type 1 (AT1) receptor antagonist candesartan blunted this increase. Moreover, the blockade of NMDA or AMPA/kainate receptors in the RVLM caused a depressor response in this SIH rat model. They concluded that AT1 receptor antagonists downregulate enhanced glutamatergic activity in the RVLM and hypothesized that central angiotensin II (Ang II) may elicit local release of glutamate via AT1 receptors, resulting in the activation of glutamatergic neurons within the RVLM, thereby increasing sympathetic tone.

AT1 receptors are expressed on both glutamatergic and GABAergic neuronal cell bodies within the RVLM, as well as on glutamatergic projections from the PVN and GABAergic projections from the CVLM [2]. This suggests that the AT1-receptor-mediated effect of brain Ang II on the RVLM may depend on a balance between the activation of glutamatergic neurons and the activation of GABAergic neurons. GABAergic neurons located within the CVLM project to the RVLM, where they have potent inhibitory actions through the stimulation of functional GABA receptors, thereby decreasing the output of the RVLM to the sympathetic preganglionic regions [2]. Our results are in line with the hypothesis that the well-documented hypertensive response to Ang II within the RVLM is mediated by the stimulation of presynaptic AT1 receptors located on glutamatergic nerve terminals, resulting in increased local glutamate release. However, the present preliminary results do not exclude that interaction with AT1 receptors on GABAergic nerve terminals originating from the CVLM, resulting in decreased GABAergic activity and subsequent disinhibition of the glutamatergic RVLM neurons, might also play a role in the AT1-receptor-mediated increase in sympathetic activity.

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Authors and Affiliations

  1. Research Group Experimental Pharmacology, Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Center for Neurosciences, VUB, Brussel, Belgium

    Laura Légat, Ilse Smolders & Alain G. Dupont

  2. Research Group Clinical Pharmacology and Clinical Pharmacy, VUB, Brussel, Belgium

    Laura Légat & Alain G. Dupont

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  1. Laura Légat
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Correspondence to Laura Légat.

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Légat, L., Smolders, I. & Dupont, A.G. Angiotensin-II-mediated AT1 receptor stimulation increases glutamate release within the rostral ventrolateral medulla of normotensive rats. Hypertens Res 43, 848–850 (2020). https://doi.org/10.1038/s41440-020-0419-z

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