Inhibition of cyclooxygenase2 causes a decrease i

Authors: Tomasz Przygodzki Marcin Talar Patrycja Przygodzka Cezary Watala

Publish Date: 2015/05/05

Volume: 71, Issue: 3, Pages: 351-358

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Abstract

Several lines of evidence suggest that cyclooxygenase2 COX2 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 COX2 has been suggested to compensate for decreased synthesis of nitric oxide NO The study investigates whether inhibition of COX2 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 COX2 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 COX2 inhibition decreased production of both prostaglandins to similar levels in both groups The use of ONO1301 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 COX2 contribution to vasodilation in diabetic animals appears to be partially a result of increased COX2dependent synthesis of PGE2 and also may be caused by impaired vasodilation mediated by the prostacyclin receptorThis work was supported by the grants from the Ministry of Science and Higher Education No N401 265839 and the National Science Centre No UMO2012/06/A/N25/00069 partly by the projects POIG01030110129/0800 and POIG 01010200069/0900 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 50264021

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