Endothelium-dependent relaxation is impaired in Schlager hypertensive (BPH/2J) mice by region-specific mechanisms in conductance and resistance arteries

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dc.contributor.authorJelinic, M.
dc.contributor.authorJackson, K.L.
dc.contributor.authorO'Sullivan, K.
dc.contributor.authorSingh, J.
dc.contributor.authorGiddy, T.
dc.contributor.authorDeo, M.
dc.contributor.authorParry, L.J.
dc.contributor.authorRitchie, R.H.
dc.contributor.authorWoodman, O.L.
dc.contributor.authorHead, G.A.
dc.contributor.authorLeo, C.H.
dc.contributor.authorQin, C.X.
dc.date.issued2023
dc.description.abstractAims: Endothelial dysfunction and arterial stiffness are hallmarks of hypertension, and major risk factors for cardiovascular disease. BPH/2J (Schlager) mice are a genetic model of spontaneous hypertension, but little is known about the vascular pathophysiology of these mice and the region-specific differences between vascular beds. Therefore, this study compared the vascular function and structure of large conductance (aorta and femoral) and resistance (mesenteric) arteries of BPH/2J mice with their normotensive BPN/2J counterparts. Main methods: Blood pressure was measured in BPH/2J and BPN/3J mice via pre-implanted radiotelemetry probes. At endpoint, vascular function and passive mechanical wall properties were assessed using wire and pressure myography, qPCR and histology. Key findings: Mean arterial blood pressure was elevated in BPH/2J mice compared to BPN/3J controls. Endothelium-dependent relaxation to acetylcholine was attenuated in both the aorta and mesenteric arteries of BPH/2J mice, but through different mechanisms. In the aorta, hypertension reduced the contribution of prostanoids. Conversely, in the mesenteric arteries, hypertension reduced the contribution of both nitric oxide and endothelium-dependent hyperpolarization. Hypertension reduced volume compliance in both femoral and mesenteric arteries, but hypertrophic inward remodelling was only observed in the mesenteric arteries of BPH/2J mice. Significance: This is the first comprehensive investigation of vascular function and structural remodelling in BPH/ 2J mice. Overall, hypertensive BPH/2J mice exhibited endothelial dysfunction and adverse vascular remodelling in the macro- and microvasculature, underpinned by distinct region-specific mechanisms. This highlights BPH/ 2J mice as a highly suitable model for evaluating novel therapeutics to treat hypertension-associated vascular dysfunction.
dc.description.statementofresponsibilityMaria Jelinic, Kristy L. Jackson, Kelly O, Sullivan, Jaideep Singh, Thomas Giddy, Minh Deo, Laura J. Parry, Rebecca H. Ritchie, Owen L. Woodman, Geoffrey A. Head, Chen Huei Leo, Cheng Xue Qin
dc.identifier.citationLife Sciences, 2023; 320
dc.identifier.doi10.1016/j.lfs.2023.121542
dc.identifier.issn0024-3205
dc.identifier.issn1879-0631
dc.identifier.orcidParry, L.J. [0000-0002-6883-3418]
dc.identifier.urihttps://hdl.handle.net/2440/138176
dc.language.isoen
dc.publisherElsevier BV
dc.relation.grantNHMRC
dc.rights© 2023 Elsevier Inc. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.lfs.2023.121542
dc.subjectEndothelial dysfunction
dc.subjectHypertension
dc.subjectNitric oxide
dc.subjectPassive mechanics
dc.subjectProstanoids
dc.subjectVascular compliance
dc.subject.meshArteries
dc.subject.meshMesenteric Arteries
dc.subject.meshEndothelium, Vascular
dc.subject.meshSympathetic Nervous System
dc.subject.meshEndothelium
dc.subject.meshAnimals
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshProstatic Hyperplasia
dc.subject.meshHypertension
dc.subject.meshBlood Pressure
dc.subject.meshVasodilation
dc.subject.meshMale
dc.titleEndothelium-dependent relaxation is impaired in Schlager hypertensive (BPH/2J) mice by region-specific mechanisms in conductance and resistance arteries
dc.typeJournal article
pubs.publication-statusPublished

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