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Relaxation Effect of Abacavir on Rat Basilar Arteries
- Source :
- PLoS ONE, PLoS ONE, Vol 10, Iss 4, p e0123043 (2015)
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 2015.
-
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 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.
- Subjects :
- Adenosine monophosphate
medicine.medical_specialty
Nucleotidase activity
Muscle Relaxation
Vasodilator Agents
lcsh:Medicine
Muscle, Smooth, Vascular
chemistry.chemical_compound
Adenosine Triphosphate
Risk Factors
immune system diseases
Abacavir
Internal medicine
Nucleotidase
medicine
Animals
Humans
lcsh:Science
Cyclic GMP
Cyclic guanosine monophosphate
Multidisciplinary
business.industry
lcsh:R
Myography
virus diseases
Adenosine
Adenosine receptor
Dideoxynucleosides
Rats
Muscle relaxation
Endocrinology
chemistry
Cardiovascular Diseases
Basilar Artery
lcsh:Q
business
Research Article
Muscle Contraction
medicine.drug
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....c08325a194d60d1eca12a38c16aa85fb