DPP‐4 inhibitor linagliptin restores endothelium‐dependent relaxation in small mesenteric artery from type‐1 diabetic rats (1051.4)

Abstract

Dipeptidyl peptidase‐4 (DPP‐4) inhibitors which are used to treat hyperglycaemia in type 2 diabetes may exert beneficial cardiovascular effects independently of their glucose lowering action. We hypothesized that linagliptin (LNG) treatment (4 weeks, 2 mg/kg per day orally) would improve relaxation in mesenteric arteries (MA) from STZ‐induced diabetic rats. In MA from diabetic rats there was a significant increase in superoxide levels, assayed by lucigenin chemiluminescence (diabetes, 1448± 108 counts/mg versus normal 644±380 counts/mg, n=7‐9, p<0.01). LNG does not reduce high blood glucose levels in diabetic rats (diabetes, 25±2.2 mM versus diabetes+ LNG, 27±1.7 mM). Acetylcholine (ACh)‐induced relaxation of MA was assessed using wire myography (pEC50=7.26±0.13, n = 8). Diabetes significantly reduced the sensitivity to ACh and treatment with LNG improved endothelial dysfunction (pEC50, diabetic 6.15±0.21 versus diabetic+ LNG, 6.84±0.13, n=8‐10, p<0.05). Diabetes impaired the contribution of both NO and EDHF to ACh‐induced relaxation and LNG treatment significantly enhanced the contribution of both relaxing factors. Our results indicate that the treatment of diabetic rats with LNG significantly reduced vascular superoxide levels and preserved both NO and EDHF mediated relaxation indicating that LNG can improve endothelial function in diabetes independently of any glucose lowering activity.