Role of P2X1 receptor on impaired vascular responses in experimental diabetes rat model

Objective: Diabetes Mellitus (DM) causes serious disorders of the cardiovascular system. Purinergic receptors are important regulators of vascular tone. The P2X receptor is found in vascular endothelial and smooth muscles and its effect on vascular tone in the DM rat model is unknown in this study, we aimed to investigate the vascular responses mediated by P2X1 receptor activation in STZ induced diabetes mellitus model. Method: Animals were randomly divided into two groups as Diabetes (DM) and Control (C). In order to induce diabets, 65 mg/kg dose of streptozotocin was i.p. injected to animals of DM group and After 12 weeks of the STZ injection, second branchs of the mesenteric artery were obtained from all animals and placed in the wire myograph in order to evaluate the vascular responses to ATP, and P2X1 receptor agonist, in the presence and absence of P2X1 receptor antagonist. Vascular responses were examined using eNOS, COX-2 and K+ channel inhibitors in order to determine the mechanism by which relaxation was obtained. Results: In DM group relaxation responses to P2X1 receptor agonist were lower compared to C group. These relaxation responses were significantly suppressed in both groups in responseto P2X1 receptor antagonist. In the presence of COX-2 inhibitor indomethacin, no significant reduction in relaxation responses was observed in both groups, whereas relaxation responses in both groups decreased in the presence of eNOS inhibitor L-NAME. Additionally, there was no significant difference in the relaxation responses in the presence of K+ channel inhibitors, TEA and apamine, in C-group animals. However, these inhibitors cause a significant decrease in vascular relaxation in DM group rats. Conclusion: Results of this study demonstrate that P2X1 mediated relaxation responses impaired in STZ induced DM model. The relation between diabetes and P2X1 receptor will provide a better understanding of purinergic signalling's role in the diabetes mediated vascular complications.