Brain AT1 and AT2 receptors and nitric oxide in baroreflex regulation of renal sympathetic activity in unanaesthetised rats

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dc.contributor.authorAbdulla, M.H.
dc.contributor.authorJohns, E.J.
dc.contributor.funderWellcome Trust
dc.date.accessioned2026-10-21T11:53:01Z
dc.date.available2026-10-21T11:53:01Z
dc.date.issued2025-11-26
dc.description.abstractThis study investigated the role of brain AT1 and AT2 receptors and the nitric oxide (NO) system in modulating renal sympathetic nerve activity (RSNA) baroreflex in unanaesthetised rats. Baroreflex gain curves (BRC) were generated following intracerebroventricular (I.C.V.) infusion of saline, Ang II, or Ang II combined with either losartan, PD123319 (AT2 antagonist), or L-NAME (NO synthase inhibitor). An AT2 agonist (CGP42112) was also infused I.C.V. with L-NAME. RSNA baroreflex sensitivity increased by 60% (P = 0.004) following losartan compared to saline (-4.8 ± 1.9 vs. -3.0 ± 0.9), but not after CGP42112. I.C.V. Ang II increased maximum gain by ~ 70% (P = 0.003) compared to saline (-5.0 ± 1.6 vs. -3.0 ± 0.9). This effect was reversed when Ang II was co-infused with PD123319 (-3.7 ± 1.1), but not losartan. I.C.V. CGP42112 increased the overall response range of the baroreflex but lowered the minimum level it could reach compared to saline (P = 0.03 − 0.02). The baroreflex effects of I.C.V. CGP42112 (P = 0.013), but not Ang II, were abolished when co-infused with L-NAME. These findings demonstrate an important facilitatory role for AT2 in baroreflex regulation of RSNA in unanaesthetised rats at basal brain levels of Ang II, a mechanism that is dependent on a functional NO system. By contrast, AT1 exerts an inhibitory effect on the baroreflex that is independent of NO. These observations suggest that targeting central AT2 receptors may represent a potential therapeutic strategy for conditions such as neurogenic hypertension, where impaired baroreflex function is present.en
dc.description.versionPublished Version
dc.format.extent15
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid42141
dc.identifier.authororcidAbdulla, M.H.§0000-0001-5496-5017
dc.identifier.authororcidJohns, E.J.
dc.identifier.citationAbdulla, M H & Johns, E J 2025, 'Brain AT1 and AT2 receptors and nitric oxide in baroreflex regulation of renal sympathetic activity in unanaesthetised rats', Scientific Reports, vol. 15, no. 1, 42141, pp. 1-15. https://doi.org/10.1038/s41598-025-26231-6
dc.identifier.doi10.1038/s41598-025-26231-6
dc.identifier.endpage15
dc.identifier.issn2045-2322
dc.identifier.issued1
dc.identifier.journaltitleScientific Reports
dc.identifier.otherRIS: urn:D2B93E0DC11EC3905516E41A09C0876F
dc.identifier.otherORCID: /0000-0001-5496-5017/work/199234250
dc.identifier.startpage1
dc.identifier.urihttps://hdl.handle.net/10468/19479
dc.identifier.volume15
dc.language.isoen
dc.publisherNature Research
dc.relation.urihttps://www.scopus.com/pages/publications/105023202179
dc.rights© 2025, the Author(s). Open Access .This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/
dc.rights.accessrightsopen access
dc.rights.licensenameAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.statusPeer reviewed
dc.subjectAT2
dc.subjectAngiotensin II
dc.subjectBaroreflex
dc.subjectLosartan
dc.subjectMaximum gain
dc.subjectPD123319
dc.subjectRenal sympathetic nerve activity
dc.subject[Medicine]
dc.titleBrain AT1 and AT2 receptors and nitric oxide in baroreflex regulation of renal sympathetic activity in unanaesthetised ratsen
dc.typeArticle (peer-reviewed)
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