The effect of glyproline peptides on levels of nitric oxide metabolites and tissue plasminogen activator activity in healthy rats and rats with metabolic syndrome

Abstract

Short regulatory proline-containing peptides can exert an anticoagulation effect and be protective in thrombosis.
The aim of this study was to identify indirect effects of glyproline peptides Pro-Gly-Pro (PGP) и Arg-Glu-Arg-Pro-Gly-Pro (RERPGP) on vascular endothelial function and the fibrinolytic system in normal and impaired lipid metabolism.
Methods. Peptides were synthesized at the Institute of Molecular Genetics, Russian Academy of Sciences. Experiments were performed on 60 male Wistar rats divided into healthy animals and animals with experimental metabolic syndrome (MS). Peptides (100 μg/kg) were administered intranasally, once a day for 7 days. Blood tests were performed 20 h and 168 h after the last administration of the peptides. Concentrations of nitric oxide (NO) metabolites (sum plasma concentration of nitrate and nitrite) and the activity of tissue plasminogen activator (TAP) were measured.
Results. The effects of PGP and RERPGP on the endothelial function in healthy animals were different. Significant increases in both TAP activity and NO metabolite concentration were found in plasma 20 h after 7 PGP administrations, which persisted throughout 168 h of the experiment. Only an increase in nitrate/nitrite was observed at 168 h after the RERPGP administration. PGP also exerted pronounced effects on the endothelial function, including in MS. TAP activity was significantly increased at 20 h after 7 administrations of the peptide, and this effect remained at 168 h after the PGP administration. These values were practically similar to the TAP values in healthy rats. Concentrations of NO metabolites were also significantly increased after the PGP exposure of MS rats. Possible mechanisms for the peptide activation of vascular endothelium are discussed.
Conclusion. Glyproline peptides had a stimulatory effect on the endothelial function both in normal and pathological conditions by increasing the TAP activity and the concentration of NO metabolites.