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.

The modern view on the role of glyprolines by metabolic syndrome.

The analysis of the literature data and own experimental studies on the effect of glyproline peptides on fat, carbohydrate metabolism, and hemostasis system when modeling metabolic syndrome in animals (rats) was carried out. Violations of fat and carbohydrate metabolism are characterized by hypercoagulation, increased glucose levels, dyslipidemia, and decreased rheological properties of blood. In this condition, the arginine- and lysine-containing glyprolines (PGP, PRP, RPGP, KKRRPGP, RKKRPGP, and KRRKPGP) at multiple (7 days) intranasal introduction had a complex effect on the hemostatic parameters, increasing antiplatelet, anticoagulant, and fibrinolytic activity of blood plasma.

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.

Effect of a New Synthetic Peptide Preparation AСTHPGP on the Hemostasis System in Rats.

We studied the effect of chronic intranasal and peroral administration of a new peptide preparation AСTHPGP 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.

The Status of the Hemostasis System under the Influence of Proline Peptides during the Development of Experimental Metabolic Syndrome.

A comparative study of the influence of regulatory proline peptides Pro-Gly-Pro, Pro-Arg-Pro, Pro-Gly-Pro-Leu, and Arg-Pro-Gly-Pro on the state of the hemostasis system was carried out in an experiment on male rats with metabolic syndrome. Under these conditions, repeated (7-fold) intranasal administration of the peptides in a daily dose of 50 μg/kg resulted in an increase in the anticoagulant potential of the blood, namely, in an increase in the anticoagulant, fibrinolytic, and antiplatelet activity 20 h and 7 days after the last peptide injection. The arginine-containing peptide Arg-Pro-Gly-Pro had the most pronounced and stable effect on haemostasis under these experimental conditions.