Publication: Effects of sitagliptin on ß-adrenoceptor mediated relaxation in streptozotocin-diabetic rat aorta
Loading...
Date
2020-11-13T00:00:00Z
Authors
Authors
Muderrisoglu, Ayhanim Elif
Erdogan, Betul Rabia
Yeşilyurt, Zeynep Elif
Uyar Boztas, Ceren
Karacomerlioglu, İrem
Altan, Vecdi Melih
Arioglu İnan, Ebru
Journal Title
Journal ISSN
Volume Title
Publisher
Metrics
Abstract
Background/aim: Dipeptidyl peptidase-4 (DPP4) inhibitors, a class of oral antidiabetic drugs, have been shown to be protective on the vascular system because of their antiinflammatory, antiatherosclerotic, and vasodilatory effects. ß2-adrenoceptors (ß2-ARs) mediate the vasorelaxation in the aorta. However, ß3-adrenoceptor-mediated relaxation has not been studied in diabetic aorta yet. Thus, we aimed to study the effect of sitagliptin treatment on ß2- and ß3-adrenoceptor-mediated relaxations in the diabetic rat aorta.
Materials and methods: Eight-week old Sprague Dawley rats were divided into three groups: control, diabetic, sitagliptin treated diabetic. Diabetes was induced by injection of streptozotocin (35 or 40 mg/kg, intraperitoneally). After 10 weeks of diabetes, some of the diabetic rats were treated with sitagliptin (orally, 10mg/kg/day). ß2- and ß3-AR-mediated relaxation responses were evaluated by using isoprenaline and CL 316,243, respectively. ß3-AR-mediated relaxation experiments were repeated in presence of L-NAME. Western blotting and immunohistochemistry were performed to determine the abundance of ß3-adrenoceptor and endothelial nitric oxide synthase (eNOS).
Results: The isoprenaline-mediated relaxation response was impaired in the diabetic group and sitagliptin treatment did not improve it. There was no significant change in CL316,243 mediated-relaxation or protein expression of ß3-ARs among the groups. However, the ratio of phosphorylated eNOS/NOS protein was increased markedly in the sitagliptin treated group, which points the stimulating effect of this drug towards the eNOS pathway.
Conclusion: Our results indicate that sitagliptin treatment does not alter ß-AR-mediated relaxation in streptozotocin-diabetic rat aorta; however, it significantly stimulates the eNOS pathway. Future studies are needed to clarify the relationship between the eNOS pathway and DPP-4 inhibition.
Description
Keywords
aorta, endothelial nitric oxide synthase, sitagliptin, streptozotocin induced diabetes, ß-adrenoceptors, streptozotocin induced diabetes