Skip to main content

Research Repository

Advanced Search

Effect of simvastatin on vascular tone in porcine coronary artery: potential role of the mitochondria

Almukhtar, H.; Garle, M.J.; Smith, P.A.; Roberts, Richard E.

Authors

H. Almukhtar

M.J. Garle

P.A. Smith

Richard E. Roberts



Abstract

Statins induce acute vasorelaxation which may contribute to the overall benefits of statins in the treatment of cardiovascular disease. The mechanism underlying this relaxation is unknown. As statins have been shown to alter mitochondrial function, in this study we investigated the role of mitochondria in the relaxation to simvastatin.
Relaxation of porcine coronary artery segments by statins was measured using isolated tissue baths. Mitochondrial activity was determined by measuring changes in rhodamine 123 fluorescence. Changes in intracellular calcium levels were determined in freshly isolated smooth muscle cells with Fluo-4 using standard epifluorescent imaging techniques.
Simvastatin, but not pravastatin, produced a slow relaxation of the coronary artery, which was independent of the endothelium. The relaxation was attenuated by the mitochondrial complex I inhibitor rotenone (10 ?M) and the complex III inhibitor myxothiazol (10 ?M), or a combination of the two. The complex III inhibitor antimycin A (10 ?M) produced a similar time-dependent relaxation of the porcine coronary artery, which was attenuated by rotenone. Changes in rhodamine 123 fluorescence showed that simvastatin (10 ?M) depolarized the membrane potential of mitochondria in both isolated mitochondria and intact blood vessels. Simvastatin and antimycin A both inhibited calcium-induced contractions in isolated blood vessels and calcium influx in smooth muscle cells and this inhibition was prevented by rotenone.
In conclusion, simvastatin produces an endothelium-independent relaxation of the porcine coronary artery which is dependent, in part, upon effects on the mitochondria. The effects on the mitochondria may lead to a reduction in calcium influx and hence relaxation of the blood vessel.

Citation

Almukhtar, H., Garle, M., Smith, P., & Roberts, R. E. (2016). Effect of simvastatin on vascular tone in porcine coronary artery: potential role of the mitochondria. Toxicology and Applied Pharmacology, 305, https://doi.org/10.1016/j.taap.2016.06.024

Journal Article Type Article
Acceptance Date Jun 21, 2016
Online Publication Date Jun 23, 2016
Publication Date Aug 15, 2016
Deposit Date Aug 3, 2016
Publicly Available Date Mar 29, 2024
Journal Toxicology and Applied Pharmacology
Print ISSN 0041-008X
Electronic ISSN 0041-008X
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 305
DOI https://doi.org/10.1016/j.taap.2016.06.024
Keywords Statins; Mitochondria; Vasodilatation
Public URL https://nottingham-repository.worktribe.com/output/805507
Publisher URL http://www.sciencedirect.com/science/article/pii/S0041008X16301582