Study of Endothelial Protective Activity of Phenol-Derived Thrombin and Arginase-2 Inhibitors KUD-259 and KUD-974.

We performed correction of endothelial dysfunction with phenol derivatives KUD-259 and KUD-974 containing heteroatomic and heterocyclic structures. Pharmacological activity of KUD-259 and KUD-974 surpassed that of L-norvaline, a non-selective arginase inhibitor.

[Correction of endothelial dysfunction by L-arginine under experimental pre-eclampsia conditions].

The ADMA-like pre-eclampsia in pregnant rats was modeled by daily introduction of L-NAME in a dose of 25 mg/kg for 7 days. L-arginine (200 mg/kg) prevented the development of arterial hypertension and a decrease in placentary microcirculation and microalbuminuria. The possibility of using L-arginine for the prevention of competitive eNOS inhibition by ADMA is discussed.

Effect of L-arginine, vitamin B6 and folic acid on parameters of endothelial dysfunction and microcirculation in the placenta in modeling of L-NAME-induced NO deficiency.

L-arginine (200 mg/kg), vitamin B(6) (2 mg/kg), and folic acid (0.2 mg/kg) exert a protective effect on endothelial function in L-NAME-induced NO deficiency in male and pregnant female Wistar rats. Combined administration of these agents effectively prevented the development of endothelial dysfunction and L-NAME-induced preeclampsia.

A model of hyperhomocysteine-induced endothelial dysfunction in rats.

Intragastric methionine (3 g/kg daily for 7 days) elevates homocysteine concentration and increases the endothelial dysfunction coefficient. This protocol of methionine treatment is an adequate model of hyperhomocysteine-induced endothelial dysfunction and can be used for studies of the endothelio- and cardioprotective effects of drugs.

Assessment of the Nephroprotective Properties of the Erythropoietin Mimetic Peptide and Infliximab in Kidney Ischemia-Reperfusion Injury in Rats.

Chronic kidney disease (CKD) or acute kidney injury (AKI) causes impaired kidney function, leading to cognitive impairment, neuropathy, and cerebrovascular disease. Due to kidney damage, toxins stay in the blood rather than leaving the body through the urine, and brain function is affected by kidney-brain interaction. The present study aimed to investigate the protective effects of erythropoietin mimetic peptide (pHBSP) and infliximab on ischemic renal reperfusion injury. The experiment was performed on 70 white male Wistar laboratory rats which received recombinant erythropoietin, pHBSP, and infliximab. Under anesthesia, traumatic vascular clamps were applied to the left renal pedicle for 40 min, and nephrectomy was performed on the right. Functional tests and laboratory tests were performed 5 min and 24 h after the reperfusion.  Thereafter, 24 h after the surgery, the plasma creatinine and urea levels in the sham-operated animals were obtained at 45.9±0.8 mmol/L and 6.7±0.2 mmol/L, respectively. Plasma creatinine and urea levels in the control group animals were 102.63±3.6 mmol/L and 21.80±1.29 mmol/L, respectively. The administration of pHBSP and infliximab to the animals with ischemia-reperfusion kidney injury has a pronounced nephroprotective effect, as compared to erythropoietin. There was a significant decrease in blood levels of creatinine and urea, improvement of microcirculation in the kidney, normalization of glomerular filtration rate, and fractional sodium excretion. The results of the study demonstrated pointed to the prospects of pHBSP and infliximab administration in ischemia-reperfusion kidney injury and justified the feasibility of further research in this field.

[Integrated assessment of endothelio- and cardioprotective activity of macrolide antibiotics in nitric oxide deficiency model].

Experiments on laboratory animals with nitric oxide deficiency modeled by the introduction of L-NAME (NO-synthase inhibitor) revealed the endothelio- and cardioprotective effects of clarithromycin, josamycin, roxithromycin, midecamycin and azythromycin. The administration of these macrolides leads to a decrease in the resulting area of the diagram of functional indices of the state of vessels and myocardium, which is approaching the corresponding area for intact animals.

[Experimental study of cardioprotective and endothelioprotective action of macrolides and azalides].

The cardioprotective and endothelioprotective effects of the macrolide antibiotics roxithromycin, azythromycin, and midecamycin have been studied on laboratory animals with models of the coronaro-occlusional myocardial infarction and endothelial dysfunction. The drugs led to a dose-dependent decrease in lethality, reduced the zone of necrosis of the left ventricle after coronary occlusion, and produced a positive effect on the functioning of endothelium.