Antioxidant Defense System after Single and Chronic Administration of Obestatin and Its Fragment (1-4) to Normal and Overweight Male Rats.

We studied the effects of anorectic peptide obestatin and its fragment (1-4) on the antioxidant defense system in animals with normal and experimentally induced increased body weight. In rats with normal body weight, no changes in activity of the antioxidant defense system 1 week after single administration of the substances. After chronic administration of obestatin and fragment (1-4) for 1 week, total antioxidant capacity of the plasma decreased; obestatin also lowered the content of TBA-reactive products. In the overweight rats, SOD-like activity in the plasma increased 1 week after chronic administration of obestatin. Hence, obestatin and its fragment (1-4) induced changes in the antioxidant defense system only after chronic administration.

Effect of anorexigenic peptide obestatin on platelet aggregation and osmotic resistance of erythrocytes.

We studied the effects of the anorexigenic peptide obestatin on the coagulation system and blood rheology (by the parameters of platelet aggregation and osmotic resistance of erythrocytes) in vitro and in vivo. Obestatin inhibited in vitro platelet aggregation in the entire dose range and reduced osmotic resistance of erythrocytes in all doses except 300 nmol/kg (obestatin in a dose of 300 nmol/kg had no effect on this parameter). Similar to the results of in vitro experiments, intranasal, intraperitoneal, and subcutaneous administration of obestatin in a dose of 300 nmol/kg inhibited platelet aggregation and had no effect on the osmotic resistance of erythrocytes.

Tripeptide Pro-Gly-Pro prevents disturbances in osmotic resistance of rat erythrocytes under conditions of inflammation.

The development of inflammation (experimental model of peritonitis induced by administration of sodium thioglycolate) was accompanied by a decrease in osmotic resistance of erythrocytes. Changes in osmotic resistance of erythrocytes associated with preliminary (15 min before induction of inflammation) administration of peptide Pro-Gly-Pro were significantly weaker, and the percentage of hemolyzed cells was reduced. The peptide injected against the background of developed inflammation (1 h 45 min after induction) had no corrective effect on osmotic resistance. During in vitro experiments, Pro-Gly-Pro did not affect hemolysis of intact erythrocytes. These results support the assumption that prophylactic administration of the peptide protects erythrocyte membranes and increases their osmotic resistance.

[Functional activity of vasopressin analog desglycinamide-arginine-vasopressin].

Original and published data on the functional activity of neurohypophyseal hormone vasopressin and its analog DGAVP were analyzed with a particular focus on the pattern of the peptide effect on the hemostatic system. The effects of the natural hormone and its synthetic analog on some indices of coagulation and fibrinolysis were compared. The effects of the peptides on the behavioral responses as well as on memory processes of animals are analyzed.

Correction of changes in ADP-induced platelet aggregation with vasopressin analogue desglycinamide-arginine-vasopressin.

We studied the effect of vasopressin analogue desglycinamide-arginine-vasopressin on changes in platelet hemostasis produced by intragastric administration of Ticlid or clopidogrel (inhibitors of ADP-induced platelet aggregation). Intranasal administration of the peptide under conditions of hemorrhagic diathesis produced a hemostatic effect and normalized some parameters of blood coagulation.

[Effect of thyrotropin-releasing hormone and its synthetic analogue digipramine on certain hemostatic indices in vitro and in vivo].

The effect of neuropeptide thyrotropin-releasing hormone (TRH) and its synthetic analogue digipramine on certain indices of the blood coagulation system and fibrinolysis were studied in vitro and in vivo. The peptides added to the pool of normal rat plasma at 10(-10) to 10(-3) M increased the procoagulant activity but had virtually no effect on fibrinolysis. Intravenous administration of TRH and digipramine increased the procoagulant activity of the blood and thrombocyte aggregation but decreased fibrinolysis; digipramine had a more pronounced effect on the coagulation potential of the blood and a less pronounced effect on fibrinolytic indices as compared to TRH. Intranasal administration of the peptides did not change the pattern of their effect on hemostatic indices although the effects became less pronounced.

[Role of glycine in blood coagulation processes]. / Rol' glitsina v protsessakh svertyvaniia krovi.

We studied hemocoagulation properties of the amino acid glycine in vitro and after intravenous administration in animals (rats). Addition of 10(-3) and 10(-4) M glycine to the plasma increases the aggregability of thrombocytes in vitro, while all other tested concentrations had virtually no effect on hemostatic parameters of the plasma. Intravenous administration of glycine increased functional activity of the enzyme fibrinolytic unit of the anticoagulation system. Dose dependence of this effect has been established. The causes of these changes and possible application of this compound for activation of fibrinolysis are discussed.

[Effects of neurohypophysial hormones and their synthetic analogs on platelet aggregation]. / Vliianie neirogipofizarnykh gormonov i ikh sinteticheskikh analogov na agregatsiiu trombotsitov.

The effect of neurohypophysial hormones vasopressin and oxytocin as well as their synthetic analogs on platelet aggregation induced by thrombin or ADP was studied in vitro on washed rat platelets. Vasopressin and its analog DGAVP, as well as oxytocin enhanced thrombin-induced platelet aggregation, while their effect on ADP-induced aggregation was considerably lower. An oxytocin analog depotocin had a pronounced antithrombin effect indicated by a significant inhibition (by 81%) of thrombin-induced platelet aggregation and by assay for its antithrombin activity in the blood plasma.

[The effect of modified forms of vasopressin on the rat hemostatic system]. / Vliianie modifitsirovannykh form vazopressina na sistemu gemostaza krys.

The effect of modified forms of vasopressin (MFV) that do not possess hormonal activity on homeostasis in rats was studied. One of the major effects of vasopressin (AVP) and its analogs on the blood clotting system, changes in fibrinolytic activity (FA) and the activity of plasminogen activator (APA), depends on modifications of the amino acid sequence in the peptide molecule. The presence of glycinamide in the AVP molecule enhances FA and APA. AVP molecules without the glycinamide group exert a more marked influence on procoagulant activity in blood.

[Thrombosis prophylaxis using plasmin and its combination with alpha-adrenoreceptor antagonists]. / Profilaktika tromboobrazovaniia s pomoshchíu plasmina i ego kombinatsii s a-adrenoblokatorami.

Using two models of experimental thrombosis (arterio-venous shunt and Wessler's model) the effect of plasmin and its combination with alpha-adrenoreceptor antagonists on the formation of thrombus was studied on white rats. It was established that the efficacy of prophylactic of thrombosis by plasmin only was low: middle ball of thrombosis was 2.5-3.0. The combination of plasmin with alpha-adrenoblockers dihydroergotoxine or prazosin under these conditions is most efficient against the formation of thrombus (middle ball of thrombus in this case was 0.8-1.1). Prazosin under certain conditions have some advantages.

[Structure-activity determination of physiological reactions of vasopressin and its analogs on the hemostasis system]. / Strukturno-funktsional'naia obuslovlennost' fiziologicheskikh reaktsiivasopressina i ego analogov na sistemu gemostaza.

Effects of vasopressin, its C-terminal fragments and derivatives on the system of hemostasis were studied in rats. Modification of amino acid sequence in vasopressin molecule led to distinct alterations in main peptide properties. Presence of ring structure in the peptide molecule appears to be obligatory to increase the content of factor VIII in blood, while absence of glycine in side chain caused a decrease in the rate of fibrinolysis and in activity of plasminogen activators.

[Effect of vasopressin and its analogs on blood coagulation in rats]. / Vliianie vazopressina i ego analogov na svertyvanie krovi u krys.

A change in the response of the blood coagulation system to the intravenous injection of vasopressin (AVP), DDAVP and DGAVP has been studied in the experiments on white rats. Intensification of the procoagulant activity on AVP is of the dose-dependent character. Maximal effect is observed 5-15 min after i.v. injection of AVP in a dose of 4 mg/kg. The administration of this peptide increases the fibrinolytic activity, that is connected with an increase in the level of plasminogen activator. DDAVP and DGAVP have a weaker effect on fibrinolysis. AVP and DDAVP increase the level of FVIII by 5-6% during the first minutes, but DGAVP increases the level of FVIII only after 15-30 minutes. While using AVP, DDAVP and DGAVP in clinical practice it is necessary to allow for their hormonal action, the initial state of haemostasis and the age of patients.

[The role of cholinergic receptors in the reactions of the hemostasis system to vasopressin]. / Uchastie kholinoretseptorov v reaktsiiakh sistemy gemostaza na vazopressin.

Participation of central and peripheral++ cholinoreceptors in responses of blood coagulation system to intravenous vasopressin injection has been studied in experiments on white rats. Vasopressin was injected in combination with atropine and metacine Intensification of the procoagulant activity, that was observed 15 min after vasopressin injection (4 micrograms/kg), was practically retained during cholinergic blockade. The intensification of fibrinolytic activities as a result of an increase in the level of plasminogen activators in blood, is to a great extent blocked by atropine rather than by metacine. Consequently, to intensify the procoagulant activity without changes in fibrinolysis (for example hemophilia) it is necessary to use the vasopressin injection in combination with atropine.

[The role of the active center of the enzyme in the triggering mechanism of the compensatory reaction to plasmin]. / Rol' aktivnogo tsentra fermenta v trigernom mekhanizme kompensatornoi reaktsii na plazmin.

The participation of plasmin active site in the trigger's mechanisms of the compensatory reaction of haemostasis system on this enzyme was studied in the experiments on white rats and rabbits using intravenous injection and perfusion of the humorally isolated carotid sinus are with intact innervation. Native enzyme, the enzyme with reversibly (acylated plasmin) and irreversibly (diisopropylphosphoryl plasmin) blocked active site were used. It was ascertained that the development of the compensatory reaction of haemostasis system on plasmin, manifested by hypercoagulation and depression of fibrinolysis, is conditioned by the proteolytic activation of the vascular wall receptors.