Effect of vildagliptin on endothelium-dependent vasodilation in rat arteries and its mechanism

Abstract:

Objective：To investigate the effect of vildagliptin on vasodilation in rats and its mechanism. Methods：Male Sprague-Daw－ley rats were divided into control group（n=10） and vildagliptin group[6 mg/（kg·d），n=10]. These rats were treated for 6 months，and the thoracic aortas and mesenteric arteries were harvested at the end of the 6-month treatment for analysis. The endothelium-dependent vasodilation in the thoracic aorta and mesenteric artery was measured by wire myograph，the nitric oxide（NO） level was measured by colorimetry，and the protein and mRNA levels of endothelial nitric oxide synthase（eNOS） were determined by Western blot and RT-PCR，respectively. Results：The results showed that acetylcholine（ACh）-mediated endothelium-dependent vasodilation in the thoracic aorta and mesenteric artery was significantly different between groups（repeated measures ANOVA，F=25.388，P=0.001；F=15.713，P =0.005） and at different ACh concentrations（repeated measures ANOVA，F=664.954，P=0.000；F=440.579，P=0.000），with a significant interaction between treatment and concentration（F=5.905，P=0.002；F=8.446，P=0.000）. The maximum vasodilation of the thoracic aorta in the control group and the vildagliptin group was （84.20±1.21）% and （92.18±1.02）%，respectively（t=5.167，P=0.000）；the maxi－mum vasodilation of the mesenteric artery in the control group and the vildagliptin group was （86.57±2.21）% and （94.24±0.92）%，respectively（t=3.202，P=0.010）. The sensitivity to ACh of the arteries was improved（t=3.883，P=0.001；t= 4.459，P=0.001）. A signifi－cant increase in the NO level in the vildagliptin group was observed compared with that in the control group（t=6.019，P=0.000；t=4.848，P=0.000）. The protein level（t=6.193，P=0.000；t=4.895，P=0.001） and mRNA level（t=6.100，P=0.000；t=6.240，P=0.000） of eNOS in the thoracic aorta and mesenteric artery were up-regulated in the vildagliptin group. Conclusion：Vildagliptin can promote vasodilation in rat thoracic aorta and mesenteric artery by up-regulating eNOS transcription and expression.