Abstract
Several lines of evidence suggest that cyclooxygenase-2 (COX-2) activity can have a beneficial role in the maintenance of vascular tone of the blood vessels in diabetes. Specifically, the increased production of prostacyclin (PGI2) and prostaglandin E2 (PGE2), mediated by COX-2, has been suggested to compensate for decreased synthesis of nitric oxide (NO). The study investigates whether inhibition of COX-2 may reduce the coronary flow in diabetic animals and may also lead to decreased synthesis of prostaglandins. Mice aged 18–20 weeks were used for the study: those with leptin receptor deficiency (db/db) served as a model of diabetes while heterozygous (db/+) mice served as controls. Coronary flow was measured by the Langendorff method, and prostaglandin synthesis by myocardia was assayed in heart perfusates. COX-2 inhibition was found to reduce basal coronary flow in db/db mice but had no effect in db/+ mice. Secretion of PGE2 was found to be higher in db/db mice, while prostacyclin synthesis did not differ. COX-2 inhibition decreased production of both prostaglandins to similar levels in both groups. The use of ONO-1301, a specific agonist for the prostacyclin receptor revealed that vasodilating responses mediated by the receptor were impaired in db/db mice. The expression levels of the receptor in cardiac tissue did not differ between the groups. It is concluded that the increased COX-2 contribution to vasodilation in diabetic animals appears to be partially a result of increased COX-2-dependent synthesis of PGE2 and also may be caused by impaired vasodilation mediated by the prostacyclin receptor.
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Acknowledgments
This work was supported by the grants from the Ministry of Science and Higher Education (No. N401 265839) and the National Science Centre (No. UMO-2012/06/A/N25/00069), partly by the projects POIG.01.03.01-10-129/08-00 and POIG 01.01.02-00-069/09-00, financed by the European Regional Development Fund within the framework of the Innovative Economy Operational Programme 2007–2013, and by a research grant from the Medical University of Lodz (502-64-021).
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Tomasz Przygodzki and Marcin Talar contributed equally to this work.
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Przygodzki, T., Talar, M., Przygodzka, P. et al. Inhibition of cyclooxygenase-2 causes a decrease in coronary flow in diabetic mice. The possible role of PGE2 and dysfunctional vasodilation mediated by prostacyclin receptor. J Physiol Biochem 71, 351–358 (2015). https://doi.org/10.1007/s13105-015-0415-y
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DOI: https://doi.org/10.1007/s13105-015-0415-y