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AT1 Receptor Mediated Hypertensive Response to Ang II in the Nucleus Tractus Solitarii of Normotensive Rats Involves NO Dependent Local GABA Release.

Journal Contribution - Journal Article

Aim: It is well-established that angiotensin II exerts a dampening effect on the baroreflex within the nucleus tractus solitarii (NTS), the principal brainstem site for termination of baroreceptor afferents and which is densely populated with gamma-aminobutyric acid (GABA)ergic neurons and nerve terminals. The present study was designed to investigate whether local release of GABA is involved in the effects mediated by local angiotensin II within the NTS. Methods: In vivo microdialysis was used for measurement of extracellular glutamate and GABA levels and for infusion of angiotensin II within the NTS of conscious normotensive Wistar rats. The mean arterial pressure (MAP) and heart rate response to local infusion of angiotensin II were subsequently monitored with a pressure transducer under anesthesia. The angiotensin II type 1 receptor (AT1R) antagonist, candesartan, was used to assess whether responses were AT1R dependent and the nitric oxide (NO) synthase inhibitor, N(ω)-nitro-L-arginine methyl ester (L-NAME), was used to assess the involvement of NO in the evoked responses by infusion of angiotensin II. The MAP and heart rate responses were monitored with a pressure transducer. Results: Local infusion into the NTS of angiotensin II induced a significant to ninefold significantly increase in extracellular GABA levels; as well as MAP was increased by 15 mmHg. These responses were both abolished by co-infusion of either, the angiotensin II type 1 receptor antagonist, candesartan, or the NO synthase inhibitor, L-NAME, demonstrating that the effect is not only AT1R dependent but also NO dependent. The pressor response to angiotensin II was reversed by co-infusion with the GABAA receptor antagonist, bicuculline. Local blockade of NO synthase decreased both, GABA and glutamate concentrations. Conclusion: Our results suggest that the AT1R mediated hypertensive response to angiotensin II within the NTS in normotensive rats is GABA and NO dependent. Nitric oxide produced within the NTS tonically potentiates local GABA and glutamate release.

Journal: Frontiers in Pharmacology
ISSN: 1663-9812
Volume: 10
Number of pages: 13
Publication year:2019
Keywords:Angiotensin II, Gamma-aminobutyric acid (GABA), Mean arterial pressure, Nitric oxide, Nucleus tractus solitarii, Pharmacology & toxicology
  • ORCID: /0000-0002-2918-9703/work/107747408
  • ORCID: /0000-0003-2140-0751/work/62005202
  • ORCID: /0000-0003-1778-3366/work/60984624
  • DOI: https://doi.org/10.3389/fphar.2019.00460
  • Scopus Id: 85068539378
  • WoS Id: 000467314200001
  • ArticleNumber: 460