Vascular region-specific changes in arterial tone in rats with type 2 diabetes mellitus: Opposite responses of mesenteric and femoral arteries to acetylcholine and 5-hydroxytryptamine.

Aims: Type 2 diabetes mellitus (T2DM) ranks in the top 10 causes of mortality worldwide. The key factor of T2DM vascular complications is endothelial dysfunction. It is characterized by the vessels motor activity disruption and endothelium-derived factors imbalance. The blood vessels morphological and molecular heterogeneity greatly affects the changes occurring in T2DM. Therefore, we conducted a comparative study of vascular bed changes occurring in T2DM.

Main Methods: Male Wistar rats were fed a high-fat diet for 20 weeks, followed by a single streptozotocin injection (20 mg/kg). T2DM was confirmed with an oral glucose tolerance test.

Key Findings: A dose-dependent contraction study showed an increase in third-order mesenteric arterioles response to serotonin but not to phenylephrine. These vessels also exhibited a decrease in acetylcholine-dependent relaxation and an increase in guanylate cyclase function. At the same time, the femoral arteries showed a tendency for increased acetylcholine-dependent relaxation. The blood plasma analysis revealed low bioavailable nitric oxide and high levels of endothelin-1 and ROS.

Significance: This knowledge, in conjunction with the features of the T2DM course, can allow further targeted approaches development for the prevention and treatment of vascular complications occurring in the disease.