Work

The sodium-glucose cotransporter-2 inhibitor canagliflozin alleviates endothelial dysfunction in a rat bypass model

Year: 2025

Type: article

Abstract: Ischemia/reperfusion (IR) injury during coronary artery bypass grafting surgery has detrimental impacts on endothelial integrity and function. Studies have suggested that canagliflozin (CANA) mitigates the risk of cardiovascular events, independently of diabetes. We hypothesized that the supplementation and/or administration of CANA protects vascular grafts in a bypass model in non-diabetic Lewis rats. The aortic arches of control rats (n = 9) were harvested, aortic rings were prepared, then mounted in organ baths. In the IR and IR + CANA suppl groups (n = 8/group), aortic arches were preserved in either saline or CANA-supplemented saline (5 µM) for 1 h at 4 °C before transplantation. In the IR + CANA inject and IR + CANA suppl+inject groups (n = 9/group), aortic arches were preserved in cold saline or CANA for 1 h and recipients received CANA (10 µg/kg, intravenous) 5 min prior to reperfusion. After 1 h of in vivo blood reperfusion, ex vivo vascular function was assessed and immunohistochemistry was performed. The decreased maximum relaxation (R max ) to acetylcholine in the IR group compared to controls (20 ± 3 % vs 83 ± 2 %, p < 0.05) was improved in both the IR + CANA inject (36 ± 2 % vs. 20 ± 3 %, p < 0.05) and IR + CANA suppl+inject (45 ± 3 % vs. 20 ± 3 %, p < 0.05) groups. Additionally, the IR + CANA suppl+inject rings exhibited a further increased R max to acetylcholine compared to both the IR + CANA suppl (45 ± 3 % vs. 31 ± 2 %, p < 0.05) and IR + CANA inject (45 ± 3 % vs. 36 ± 2 %, p < 0.05) groups. Increased DNA strand breaks in the IR group compared to controls were decreased in all CANA groups. The reduced immunoreactivity of CD-31 was ameliorated in the IR + CANA inject and IR + CANA suppl+inject groups. CANA alleviates endothelial dysfunction induced by IR injury in a rodent model of revascularization.

Source: Biochemical Pharmacology

DOI: 10.1016/j.bcp.2025.117601