[Influence of liposomal glucosaminyl-muramyl dipeptide on superoxide and nitric oxide production by murine macrophages].

Reactive oxygen and nitrogen intermediates are key factors in inflammatory response and antitumoral activity of macrophages. Free and liposomal N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-isoglutamine influence on murine macrophages ability to generate superoxide and nitric oxide were studied. The cells pretreated by GMDP increased superoxide generation in response to secondary stimuli (phorbol ether, lipopolysaccharide, zymosan). Encapsulation in the egg phosphatidylcholine liposomes enhanced cell sensitivity to priming effect of GMDP. The presence of liposomes (up to 0.5 mg/ml) in the medium inhibited superoxide release by macrophages probably due to participation of NO as redox-active metabolite. GMDP (up to 50 microg/ml) alone as well as GMDP with LPS treatment stimulated nitric oxide synthesis by macrophages. Liposomal GMDP at lower concentrations (up to 0.02 microg/ml) enhanced macrophage response to LPS. In contrast, NO-synthetic activity of LPS-stimulated cells decreased along with the increase of liposomal GMDP concentration (up to 0.5 microg/ml). The conditions for effective use of liposomal GMDP in immunotherapy are discussed.

[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.

[Mechanisms of nitric oxide activity in cardiovascular system as a basis of pathogenetic therapy of related diseases]. / Fundamental'ni mekhanizmy diï oksydu azotu na sertsevo-sudynnu systemu iak osnovy patohenetychnoho likuvannia ïï zakhvoriuvan'.

General characteristics and mechanisms of effects of nitric oxide (NO) and its role in the development of pathology are reviewed. Presented are the data about NO participation in the regulation of circulation and cardiovascular system; NO-dependent mechanism of regulation of cardiovascular reactivity against the background of dysfunction of endothelium; cGMP-independent mechanism of NO effect upon Ca homeostasis and the sensitivity of myofibrils of smooth muscle cells to Ca ions; pharmacological correction of disturbances of NO metabolism and related endothelial dysfunction; role of age changes of the endothelial function in the development of cardiovascular pathology.

[Effect of inhibition of glycolysis and myoendothelial electrical coupling on contractile responses of pulmonary artery and aorta during hypoxia in rats]. / Vplyv blokady hlikolizu ta mioendotelial'noho elektrychnoho zv'iazku na rozvytok skorotlyvykh reaktsii stinky lehenevykh arterii ta aorty shchuriv pid diieiu hipoksiï.

The effects of blockade of glycolysis on the contractile activity of isolated vascular rings of both the pulmonary artery and, the thoracic aorta were studied under hypoxia in intact, denuded vessels and those with blocked myoendothelial electrical coupling. The blockade of glycolysis led to a reversion of a hypoxic contraction in the pulmonary artery but had no effect on hypoxic dilatation of the aorta. Hypoxic constriction of the pulmonary artery was abolished after denudation and stayed unchanged at the following blockade of glycolysis. Moreover, blockade of glycolysis had no effect on the hypoxic responses of the pulmonary artery after blockade of the myoendothelial gap junctions. The data suggest that hypoxic contraction of the pulmonary artery is endothelium-dependent, in contrast to the hypoxic dilatation of the aorta. It is likely that glycolysis in endothelial cells and myoendothelial gap junctions contribute to hypoxic pulmonary vasoconstriction due to formation and conduction the depolarizing electrical signals from endothelial cells to smooth muscles causing their contraction under hypoxia.

[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.

[cGMP-independent effect of nitric oxide on contractility and intracellular calcium level of rat tail artery vascular smooth muscles]. / tsHMF-nezalezhnyi vplyv oksydu azotu na skorotlyvu aktyvnist' i vmist vnutrishn'oklitynnoho Ca(2+) hladen'kykh m'iaziv khvostovoï arteriï shchura.

The effects of nitric oxide (NO, 10(-6) M) on contractility and intracellular calcium level ([Ca2+]i) of rat tail artery smooth muscles in control and under inhibition of soluble guanylate cyclase (sGC) with 6-anilino-5,8-quinolinedione (LY83583, 10(-6) M) are investigated. NO-induced relaxations of vascular smooth muscles comprised 61.01 +/- 5.56% of maximum induced amplitude of K(+)-contracture, and decreases in [Ca2+]i comprised 66.35 +/- 11.33%. Under the inhibition of sGC with LY83583 NO-induced relaxations of vascular smooth muscles comprised 29.41 +/- 5.17% of maximum induced amplitude of K(+)-contracture, and decreases in [Ca2+]i comprised 53.68 +/- 16.93%. Thus, cGMP-independent relaxation of vascular smooth muscle and decrease in [Ca2+]i of rat tail artery is confirmed.

[Antiprotease activity of the inhibitor from dog submandibular salivary glands]. / Antiproteazna aktivnist' ingibitora z pidshchelepnikh slinnikh zaloz sobaki

The influence of trielin, an inhibitor from dog submandibular salivary glands, was studied as applied to the activity of elastase, trypsin and chemotrypsin determined by their degrading action on protein and synthetic substrates. The inhibition constants were calculated for the enzymes. The inhibitory effect of trielin was especially developed on the trypsin when using N-alpha-benzoyl-arginine-p-nitroanilide as a substrate. On the basis of inhibition constants the affinity of different substrates to elastase trypsin and chemotrypsin was shown.