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Updated: Apr 13, 2026
Ultrasound Based Assessment of Coronary Artery Flow and Coronary Flow Reserve Using the Pressure Overload Model in Mice
Published on: April 13, 2015
Inhibition of cyclooxygenase-2 causes a decrease in coronary flow in diabetic mice. The possible role of PGE2 and
Tomasz Przygodzki1, Marcin Talar, Patrycja Przygodzka
1Department of Haemostasis and Haemostatic Disorders, Chair of Biomedical Sciences, Medical University of Lodz, Lodz, 92-215, Poland, tomasz.przygodzki@umed.lodz.pl.
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.
Insights
Cyclooxygenase-2 (COX-2) inhibition reduced coronary flow in diabetic mice, suggesting its vital role in maintaining vascular tone. Impaired prostacyclin receptor function also contributes to vasodilation issues in diabetes.
Area of Science:
- Cardiovascular Research
- Endocrinology
- Pharmacology
Background:
- Cyclooxygenase-2 (COX-2) activity may support vascular tone in diabetes by increasing prostacyclin (PGI2) and prostaglandin E2 (PGE2) production, potentially compensating for reduced nitric oxide (NO).
- Investigating COX-2's role is crucial for understanding diabetic cardiovascular complications.
Purpose of the Study:
- To determine if COX-2 inhibition affects coronary flow and prostaglandin synthesis in diabetic animal models.
- To explore the contribution of COX-2-derived prostaglandins and prostacyclin receptor signaling to vasodilation in diabetes.
Main Methods:
- Utilized leptin receptor-deficient (db/db) mice as a diabetes model and heterozygous (db/+) mice as controls.
- Measured coronary flow using the Langendorff method and quantified myocardial prostaglandin synthesis in heart perfusates.
- Assessed vasodilating responses using a prostacyclin receptor agonist (ONO-1301) and measured receptor expression levels.
Main Results:
- COX-2 inhibition significantly reduced basal coronary flow in db/db mice but not in controls.
- db/db mice exhibited higher PGE2 secretion, while PGI2 levels did not differ; COX-2 inhibition normalized prostaglandin production in both groups.
- Vasodilation mediated by the prostacyclin receptor was impaired in db/db mice, despite similar receptor expression levels.
Conclusions:
- Increased COX-2 activity contributes to vasodilation in diabetic animals, partly via enhanced PGE2 synthesis.
- Impaired prostacyclin receptor-mediated vasodilation is another significant factor in diabetic vascular dysfunction.
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