Abstract
Aim:
Metabolic syndrome (MS) and aging are low-grade systemic inflammatory conditions, and inflammation is a key component of endothelial dysfunction. The aim of this study was to investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) upon the vascular reactivity in aging MS rats.
Methods:
MS was induced in young male rats by adding 30% sucrose in drinking water over 6, 12, and 18 months. When the treatment was finished, the blood samples were collected, and aortas were dissected out. The expression of COX isoenzymes and PLA2 in the aortas was analyzed using Western blot analysis. The contractile responses of aortic rings to norepinephrine (1 μmol/L) were measured in the presence or absence of different NSAIDs (10 μmol/L for each).
Results:
Serum levels of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β) in control rats were remained stable during the aging process, whereas serum IL-6 in MS rats were significantly increased at 12 and 18 months. The levels of COX isoenzyme and PLA2 in aortas from control rats increased with the aging, whereas those in aortas from MS rats were irregularly increased with the highest levels at 6 months. Pretreatment with acetylsalicylic acid (a COX-1 preferential inhibitor), indomethacin (a non-selective COX inhibitor) or meloxicam (a COX-2 preferential inhibitor) decreased NE-induced contractions of aortic rings from MS rats at all the ages, with meloxicam being the most potent. Acetylsalicylic acid also significantly reduced the maximum responses of ACh-induced vasorelaxation of aortic rings from MS rats, but indomethacin and meloxicam had no effect.
Conclusion:
NSAIDs can directly affect vascular responses in aging MS rats. Understanding the effects of NSAIDs on blood vessels may improve the treatment of cardiovascular diseases and MS in the elders.
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Acknowledgements
This work forms part of a PhD thesis for María Esther RUBIO-RUIZ. The authors would like to thank the program of Doctorado en Ciencias Biomédicas, Facultad de Medicina UNAM. We also thank Bertha SOTO, Mario PÉREZ, Edmundo SÁNCHEZ, and Florencio HERNÁNDEZ for technical assistance.
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Rubio-Ruiz, M., Pérez-Torres, I., Diaz-Diaz, E. et al. Non-steroidal anti-inflammatory drugs attenuate the vascular responses in aging metabolic syndrome rats. Acta Pharmacol Sin 35, 1364–1374 (2014). https://doi.org/10.1038/aps.2014.67
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DOI: https://doi.org/10.1038/aps.2014.67
