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Relaxation effect of abacavir on rat basilar arteries

Li, Rachel; Yang, C; Chan, S. W.; Hoi , Maggie PM; Lee , Simon MY; Leung, George P. H.

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Background The use of abacavir has been linked with increased cardiovascular risk in patients with human immunodeficiency virus infection; however, the mechanism involved remains unclear. We hypothesize that abacavir may impair endothelial function. In addition, based on the structural similarity between abacavir and adenosine, we propose that abacavir may affect vascular contractility through endogenous adenosine release or adenosine receptors in blood vessels. Methods The relaxation...[Show more]

dc.contributor.authorLi, Rachel
dc.contributor.authorYang, C
dc.contributor.authorChan, S. W.
dc.contributor.authorHoi , Maggie PM
dc.contributor.authorLee , Simon MY
dc.contributor.authorLeung, George P. H.
dc.date.accessioned2018-11-29T22:56:10Z
dc.date.available2018-11-29T22:56:10Z
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/1885/153421
dc.description.abstractBackground The use of abacavir has been linked with increased cardiovascular risk in patients with human immunodeficiency virus infection; however, the mechanism involved remains unclear. We hypothesize that abacavir may impair endothelial function. In addition, based on the structural similarity between abacavir and adenosine, we propose that abacavir may affect vascular contractility through endogenous adenosine release or adenosine receptors in blood vessels. Methods The relaxation effect of abacavir on rat basilar arteries was studied using the myograph technique. Cyclic GMP and AMP levels were measured by immunoassay. The effects of abacavir on nucleoside transporters were studied using radiolabeled nucleoside uptake experiments. Ecto-5′ nucleotidase activity was determined by measuring the generation of inorganic phosphate using adenosine monophosphate as the substrate. Results Abacavir induced the relaxation of rat basilar arteries in a concentration-dependent manner. This relaxation was abolished when endothelium was removed. In addition, the relaxation was diminished by the nitric oxide synthase inhibitor, L-NAME, the guanylyl cyclase inhibitor, ODQ, and the protein kinase G inhibitor, KT5820. Abacavir also increased the cGMP level in rat basilar arteries. Abacavir-induced relaxation was also abolished by adenosine A2 receptor blockers. However, abacavir had no effect on ecto-5’ nucleotidase and nucleoside transporters. Short-term and long-term treatment of abacavir did not affect acetylcholine-induced relaxation in rat basilar arteries. Conclusion Abacavir induces acute endothelium-dependent relaxation of rat basilar arteries, probably through the activation of adenosine A2 receptors in endothelial cells, which subsequently leads to the release of nitric oxide, resulting in activation of the cyclic guanosine monophosphate/protein kinase G-dependent pathway in vascular smooth muscle cells. It is speculated that abacavir-induced cardiovascular risk may not be related to endothelial dysfunction as abacavir does not impair relaxation of blood vessels. The most likely explanation of increased cardiovascular risk may be increased platelet aggregation as suggested by other studies.
dc.format.mimetypeapplication/pdf
dc.publisherPublic Library of Science
dc.sourcePLOS ONE (Public Library of Science)
dc.subjectKeywords: 1 [(2 chlorophenyl)diphenylmethyl] 1h pyrazole; 1h 1,2,4 oxadiazolo[4,3 a]quinoxalin 1 one; 4 [2 [7 amino 2 (2 furyl) 1,2,4 triazolo[2,3 a][1,3,5]triazin 5 ylamino]ethyl]phenol; 6,10 diaza 3(1,3)8,(1,4) dibenzena 1,5(1,4) diquinolinacyclodecaphane; 9 (tet
dc.titleRelaxation effect of abacavir on rat basilar arteries
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume10
dc.date.issued2015
local.identifier.absfor110302 - Clinical Chemistry (diagnostics)
local.identifier.absfor110201 - Cardiology (incl. Cardiovascular Diseases)
local.identifier.absfor111502 - Clinical Pharmacology and Therapeutics
local.identifier.ariespublicationU3488905xPUB13545
local.type.statusPublished Version
local.contributor.affiliationLi, Rachel, College of Health and Medicine, ANU
local.contributor.affiliationYang, C, Yunnan Minzu University
local.contributor.affiliationChan, S. W., The Hong Kong Polytechnic University
local.contributor.affiliationHoi , Maggie PM, University of Macau
local.contributor.affiliationLee , Simon MY, University of Macau
local.contributor.affiliationLeung, George P. H., The University of Hong Kong
local.bibliographicCitation.issue4
local.identifier.doi10.1371/journal.pone.0123043
dc.date.updated2018-11-29T08:10:24Z
local.identifier.scopusID2-s2.0-84929484689
local.identifier.thomsonID000352478400093
dcterms.accessRightsOpen Access
CollectionsANU Research Publications

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