[Hypoxic pulmonary hypertension: modern views on pathogenesis and options for rational pharmacological correction].

In the article, an analysis of the modern approaches to pharmacological correction of hypoxic pulmonary hypertension in conjunction with its development mechanisms has been performed. Promising research trends for the creation of new drugs in this field have also been reviewed.

[Hypoxic pulmonary hypertension: the role of phosphatidylcholine-specific phospholipase C].

The aim of the study was to investigate the role of phosphatidylcholine-specific phospholipase C (PC-PLC) in the development of hypoxic pulmonary hypertension. Induction of hypoxic hypoxia in rats resulted in a biphasic increase in systolic right ventricular pressure (RVP). The first phase was transient (5.4 +/- 0.9 min), while the second phase was sustained and persisted during the whole time course of hypoxia (120 min). An inhibition of cNOS with L-NAME (25 mg/kg; i.v.) did not cause any change in the nature of the hypoxic reaction, despite the RVP values were significantly higher in normoxia and hypoxia. These results demonstrate that NO synthase is not substantially involved in the hypoxic pulmonary vasoconstriction. Injection of PKC inhibitor chelerythrine (0.5 mg/kg; i.v.) prevented the development of the first phase of the RVP increase and reduced the second phase by 40%. An inhibition of PC-PLC with D609 (5 mg/kg; i.v.) completely abolished pulmonary hypertension. The results obtained suggest that PC-PLC possibly plays a key role in the development and maintenance of hypoxic pulmonary hypertension.

[Inhibition of nitric oxide synthesis during bacterial shock does not prevent development of resistant hypotension and death in rats].

The study subject was the white rat-males Wistar after intra-peritoneal injection of the mixture of St. aureus and B. pyocyaneus daily cultures in the dose calculated as 1 milliard microbial organisms of each species per 100 g b.w., as well as the vascular preparations isolated from aortas of those rats. The aim is to study nitric oxide role in the development of resistant hypotension under generalization of the purulent infection. Infection of the animals with a mixture of gram-positive and gram-negative cultures led to the development of the pathological process, which can be considered as a septic (bacterial) shock. A primary lowering of the vascular tone caused by depression of the myocardial pump and contractile functions was observed. Injection of methylene blue or NOS blockers (L-NAME, S-methyl-thiourea) to the infected animals in the moment of hypotension development caused only a short-term rise in blood pressure. Survival rate in such animals was significantly lower compared to the control infected animals. Repeated injections of those agents hastened death of the experimental animals. The experiments in vitro revealed no dilatory effect of acetylcholine with preserved sensitivity of the vascular preparations to adrenomimetics and exogenous nitric oxide in both control infected animals and animals injected with methylene blue or NOS blockers. The data obtained suggested that resistant hypertension in terminal stages of septic shock is nitric oxide-independent.

[Change in contractile vascular function in arterial hypertension of different genesis and its correction with phosphatidylcholine liposomes]. / Skorochuval'na funktsiia sudyn pry arterial'nii hipertenzïi riznoho henezu ta ïï korektsiia za dopomohoiu fosfatydylkholinovykh liposom.

We examined the effects of phosphatidylcholine liposomes (PCL) upon the contractile vascular dysfunction in spontaneously hypertensive rats (SHR) and gamma-irradiated (60Co, 6 Gy) rats and rabbits. A significant impairment of endothelium-dependent relaxation was evident in both SHR and irradiated animals. An important novel finding of these experiments is that the impairment was mainly due to the loss of NO-dependent component of relaxation, with the component of relaxation mediated by EDHF being preserved. PCL were found to restore endothelium-dependent relaxation in both SHR and the irradiated vascular tissues. It is important to note that irradiated animals exhibited distinct and sustained signs of hypertension (blood pressure (BP) increased from 122 +/- 8 to 185 +/- 6 mm Hg). Being administered in a single dose of 30 mg/kg, 1 h after irradiation, PCL prevented hypertension development in an early post-irradiated period (9 days). At a later post-irradiated period (6 months), PCL in the single dose lost such a protective effect. Single administration of PCL in SHR led to a transient decrease in BP, but their repeated daily administration caused a persistent decrease in BP up to its normalization as early as in 4 days. These results suggest that PCL possess hypotensive activities due to their ability to normalize endothelial function.

[The mechanisms of the lymph-stimulating action of liposomes]. / Vyvchennia mekhanizmiv limfostymuliuiuchoï diï liposom.

The mechanisms of lymph-stimulating action of different liposomes (lecithin-cholesterin, lecithin) were studied in the experiments on dogs. It has been shown an absence of interaction between changes in the lymph outflow rate and system circulation parameters when injecting any liposomes. Moreover, water and protein filtration from the vascular bed into the interstitial space was lowered due to liposomal injection. But oxygen tension in the muscular tissues remained on the level closed to the normal one. In contrast to the intravenous injection, the subcutaneous administration of liposomes has induced the stimulation of lymph outflow, which was more expressed on both volume (nearly by 40%) and duration (nearly by 50%). The experiments with limited and crossed blood flow have demonstrated a regional character of liposomal lymph-stimulating. The mechanisms of such liposomal action may be related to both direct action of liposomes on the lymphatic smooth muscle contractility in the lymphatic vessels and the increased lymph production in the site of liposomal injection due to free radical oxidation processes being limited in that area. The micellar form of phospholipids (essential) has demonstrated no lymph-stimulating action.

[Tetrapolar rheoplethysmography in the quantitative evaluation of blood supply in extremities]. / Vykorystannia tetrapoliarnoi reopletyzmografii dlia kilkisnoi otsinky krovopostachannia kintsivok.

The method of forearm blood flow determination, based on the tetrapolar rheoplethysmography has been described. The technique offered allows one to characterize quantitatively the state of peripheric circulation. The method advantage is a simplicity and convenience of its use in physiological and clinic investigations.