dc.contributor.author | Shamsaldeen, Yousif | |
dc.contributor.author | Lione, Lisa | |
dc.contributor.author | Benham, Christopher | |
dc.date.accessioned | 2021-01-12T00:07:48Z | |
dc.date.available | 2021-01-12T00:07:48Z | |
dc.date.issued | 2020-12-05 | |
dc.identifier.citation | Shamsaldeen , Y , Lione , L & Benham , C 2020 , ' Dysregulation of TRPV4, eNOS and caveolin-1 contribute to endothelial dysfunction in the streptozotocin rat model of diabetes ' , European Journal of Pharmacology , vol. 888 , no. 173441 , EJP-54180R2 . https://doi.org/10.1016/j.ejphar.2020.173441 | |
dc.identifier.issn | 0014-2999 | |
dc.identifier.uri | http://hdl.handle.net/2299/23663 | |
dc.description.abstract | Endothelial dysfunction is a common complication in diabetes in which endothelium-dependent vasorelaxation is impaired. The aim of this study was to examine the involvement of the TRPV4 ion channel in type 1 diabetic endothelial dysfunction and the possible association of endothelial dysfunction with reduced expression of TRPV4, endothelial nitric oxide synthase (eNOS) and caveolin-1. Male Wistar rats (350–450 g) were injected with 65mg/kg i.p. streptozotocin (STZ) or vehicle. Endothelial function was investigated in aortic rings and mesenteric arteries using organ bath and myograph, respectively. TRPV4 function was studied with fura-2 calcium imaging in endothelial cells cultured from aortas from control and STZ treated rats. TRPV4, caveolin-1 and eNOS expression was investigated in these cells using immunohistochemistry. STZ-treated diabetic rats showed significant endothelial dysfunction characterised by impaired muscarinic-induced vasorelaxation (aortic rings: STZ-diabetics: Emax= 29.6±9.3%; control: Emax=77.2±2.5% P˂0.001), as well as significant impairment in TRPV4-induced vasorelaxation (aortic rings, 4αPDD STZ-diabetics: Emax= 56.0±5.5%; control: Emax= 81.1±2.1% P˂0.001). Furthermore, STZ-diabetic primary aortic endothelial cells showed a significant reduction in TRPV4-induced intracellular calcium elevation (P˂0.05) compared with the control group. This was associated with significantly lower expression of TRPV4, caveolin-1 and eNOS and this was reversed by insulin treatment of the endothelial cultures from STZ -diabetic rats. Taken together, these data are consistent with the hypothesis that signalling through TRPV4, caveolin-1, and eNOS is downregulated in STZ-diabetic aortic endothelial cells and restored by insulin treatment. | en |
dc.format.extent | 6367009 | |
dc.language.iso | eng | |
dc.relation.ispartof | European Journal of Pharmacology | |
dc.title | Dysregulation of TRPV4, eNOS and caveolin-1 contribute to endothelial dysfunction in the streptozotocin rat model of diabetes | en |
dc.contributor.institution | Centre for Health Services and Clinical Research | |
dc.contributor.institution | Basic and Clinical Science Unit | |
dc.contributor.institution | TRP Ion channels | |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Department of Clinical, Pharmaceutical and Biological Science | |
dc.contributor.institution | Centre for Research in Mechanisms of Disease and Drug Discovery | |
dc.description.status | Peer reviewed | |
dc.date.embargoedUntil | 2021-07-28 | |
rioxxterms.versionofrecord | 10.1016/j.ejphar.2020.173441 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |