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Relaxation effect of abacavir on rat basilar arteries
Rachel Wai Sum Li3; Cui Yang4; Shun Wan Chan2; Maggie Pui Man Hoi5; Simon Ming Yuen Lee5; Yiu Wa Kwan1; George Pak Heng Leung3
2015-04-08
Source PublicationPLoS ONE
ISSN19326203
Volume10Issue:4
Abstract

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 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 acetylcho-line-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.

DOI10.1371/journal.pone.0123043
URLView the original
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000352478400093
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
2.State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China
3.Affiliation Department of Pharmacology and Pharmacy, Faculty of Medicine, The University of Hong Kong, Hong Kong, China
4.Key Laboratory of Ethnic Medicine Resource Chemistry (Yunnan University of Nationalities), State Ethnic Affairs Commission & Ministry of Education, School of Chemistry & Biotechnology, Yunnan University of Nationalities, Kunming, China
5.Institute of Chinese Medical Sciences, University of Macau, Macao, China
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GB/T 7714
Rachel Wai Sum Li,Cui Yang,Shun Wan Chan,et al. Relaxation effect of abacavir on rat basilar arteries[J]. PLoS ONE,2015,10(4).
APA Rachel Wai Sum Li.,Cui Yang.,Shun Wan Chan.,Maggie Pui Man Hoi.,Simon Ming Yuen Lee.,...&George Pak Heng Leung.(2015).Relaxation effect of abacavir on rat basilar arteries.PLoS ONE,10(4).
MLA Rachel Wai Sum Li,et al."Relaxation effect of abacavir on rat basilar arteries".PLoS ONE 10.4(2015).
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