Participation of Nitric Oxide in the Realization of Hemostatic Effects of Glyproline Peptides.

The involvement of nitric oxide in the responses of the hemostasis system to the appearance of proline-containing peptides in the blood was studied in experiments on rats. It was shown that a single intranasal administration of peptides PGP, RPGP, and PGPL to rats led to an increase in fibrinolytic, anticoagulant, and antiplatelet potential of blood. The use of the non-selective NO-synthase blocker L-NAME almost completely inhibited the anticoagulant effects of the glyprolines. It was found that the mechanism of the anticoagulant-fibrinolytic and antiplatelet action of glyproline peptides is determined by the activation of the enzymatic pathway of nitric oxide formation. The obtained results revealed the involvement of nitric oxide in the implementation of hemostatic and vascular-endothelial functions of the organism.

Thromboelastographic Research of Arginine-, Leucine and Lysine-Containing Peptides.

Anticoagulant effects of 12 short peptides of the glyproline series - Arg-Glu-Arg-Pro-Gly-Pro (RERPGP), Arg-Glu-Arg-Val-Gly-Pro (RERVGP), Arg-Glu-Arg-Gly-Pro (RERGP), Arg-Pro-Gly-Pro (RPGP), Pro-Leu-Pro (PLP), Pro-Leu-Pro-Ala (PLPA), Pro-Gly-Pro-Leu (PGPL), Phe-Pro-Leu-Pro-Ala (FPLPA), Pyr-Arg-Pro (PyrRP), Lys-Lys-Arg-Arg-Pro-Gly-Pro (KKRRPGP), Arg-Lys-Lys-Arg-Pro-Gly-Pro (RKKRPGP), and Lys-Arg-Lys-Pro-Gly-Pro (KRKPGP) in concentrations of 10-3 and 10-2 mg/ml in vitro was demonstrated by the thromboelastographic method. The effects of 6 peptides ((RERPGP, RPGP, PLP, PLPA, RKKRPGP, and KKRRPGP) were also observed in vivo after intranasal or oral administration. Changes in the studied thromboelastographic parameters towards hypocoagulation in comparison with the control group were noted. Arginine and leucine glyprolines produced the maximum anticoagulant effect.

Effect of a New Synthetic Peptide Preparation AСTH15-18PGP on the Hemostasis System in Rats.

We studied the effect of chronic intranasal and peroral administration of a new peptide preparation AСTH15-18PGP in a dose of 100 mg/kg body weight on the state of vascular-platelet and plasma hemostasis in animals. It was found that this synthetic regulatory peptide administered intranasally can produce antiplatelet, anticoagulant, and antifibrin-stabilizing effects on the blood plasma in healthy rats. In both administration routes, the peptide induced activation of the anticoagulation system of the hemostasis by increasing enzymatic and non-enzymatic fibrinolysis; after intranasal administration, the fibrinolytic effects were more pronounced.

Anticoagulant Effects of Heparin Complexes with Prolyl-Glycine Peptide and Glycine and Proline Amino Acids.

The study demonstrates the formation of heparin complexes with prolyl-glycine peptide and proline and glycine amino acids. The method was developed for in vitro production of these complexes at 1:1 dipeptide to heparin molar ratio and 2:1 amino acid to heparin molar ratio. These complexes, unlike the constituents, proline and glycine, exhibited significant anticoagulant, antiplatelet, and fibrin-depolymerization activities of varying degree in vitro and in vivo. The heparin-dipeptide complex produced maximum effect. The dipeptide by itself also showed anticoagulant properties, but less pronounced than in the complex with heparin.

Arginine-containing tripeptide Pro-Arg-Gly is involved in the regulation of the function of anticoagulation and insular systems under persistent hyperglycemia.

Intranasal administration of regulatory peptide PRG to rats against the background of persistent hyperglycemia improves blood antiplatelet and anticoagulant-fibrinolytic potential and normalizes blood sugar in comparison with the corresponding parameters in control animals that did not receive the peptide. The fibrinolytic and antiplatelet activities of blood plasma remained elevated 6 days after peptide withdrawal against the background of unchanged glucose administration.