[Vascular reactivity and metabolism of the reactive oxygen species and nitrogen in effects of low doses of radiation].

The disturbance of endothelium-dependent and endothelium-independent vascular reactions of relaxation was registered in the preparations of aorta of radiosensitive BALB/c mice, exposed to chronic external gamma-irradiation (cumulative dose of 0.43 Sv). Low doses of radiation induced an intensive hydrolysis of membrane phospholipids by phospholipase A2, displayed by an increase in the level of eukosanoisds--LTC4 and TxB2, formed under effects of lipid oxidases (lipoxygenase and cyclooxygenase) at the same time with O2 generation. High doses of O2- can also be formed under the effect of low doses of radiation along xanthine oxidase pathway simultaneously with uric acid. In these conditions *OH-radical is formed not only at the expense of water radiolysis, which is observed under the effect of high doses, as well as along the two--NO-dependent and NO-independent--pathways. Significant increase in the content of lipid peroxidation products--dienic conjugates and valonic dialdehyde--in the organs of cardiovascular system is a confirmation of active generation of *OH and *NO2 under the effect of low doses of radiation. The latter induce significant changes in the pools of NO stable metabolites, which can cause disturbance of NO-dependent physiological functions of both heart and aorta. Significant decrease in the levels of nitrite and nitrozothiols in these conditions may result in an oxidative stress. In increased simultaneous generation of *O2- and NO they may bind and thus form a toxic substance peroxynitrite. This notion can be confirmed by the low doses of nitrite, which are formed spontaneously in the presence of molecular oxygen against the background of increased or control levels of nitrate, which is formed mainly at the degradation of peroxynitrite, i.e. at high levels of superoxide anion.

[Effect of L-arginine on the endothelium functional activity in experimental diabetes mellitus].

The experimental data about the shift of L-arginine metabolism in the direction of activization of non-oxidizing (arginase) way under experimental diabetes mellitus are presented. This shift was proved by an increase of the ratio of arginase and NO-synthase activity and an increase of the ratio of their metabolites. The decrease of the free L-arginin contents in tissues of animals with experimental diabetes mellitus is shown. The long infusion of L-arginine results in the restoration of the endothelial function, however cessation of infusion results in a gradual reduction of this effect.

Age-related changes in electrical reactions of rat aorta endothelium elicited by acetylcholine and ATP.

Age-related changes in some electrophysiological parameters of the endothelium in isolated rat aorta were studied. In comparison with young rats (6 months), resting potential of the endothelium in aged rats (24-26 months) was significantly higher and varied in a wider range. The electrical responses of intact endothelium of isolated aorta to acetylcholine were typical and regular in young rats, while in aged rats these responses were irregular and atypical. It is hypothesized that atypical electrical responses of the endothelium to acetylcholine and ATP in aged animals result from functional clustering associated with disturbances in electrical contacts between endotheliocytes. We hypothesize that the age-related decrease in NO production is related to disturbances of electrical properties of endothelial membrane.

[Effect of low doses of radiation on the contractility of vascular smooth muscle at stretch]. / Vliianie malykh doz radiatsii na sokratitel'nye otvety sosudistykh gladkikh myshts pri rastiazhenii.

The contractile reactions of the vascular smooth muscles at their stretch were studied in the isolated strips of v. porta of control rats and those, which had been born and exposed for 6 months to low intensity small dose radiation (Experimental Base in Chernobyl). The results obtained revealed the "mosaic" and significant disturbances (60% of cases) of the muscle contractile activity in the experimental animals. The myogenic mechanisms, which provide for the length-force dependence of the vessel's smooth muscles, were less effective in experimental vs. control animals. A major reason for the above changes may be the disturbances of the endothelium's function.

Length-tension dependence in vascular smooth muscle: possible participation of endothelin.

The results of experiments with isolated strips of rat portal vein, and of 'sandwich' experiments involving strips of the portal vein or aorta, revealed the involvement of endothelin in the development of myogenic reactions of the vascular smooth muscle, observed on distension of the vascular wall. Released by the endothelial cells, endothelin is capable of stimulating the contraction of these muscles.

Role of nitric oxide in myocardial reactive hyperemia in a dog.

Reactive hyperemia (RH) was produced after short-term (5-30 s) cessation of blood flow in experiments on anesthetized dogs following catheterization of the circumflex branch of the left coronary artery (with the chest intact) autoperfused with blood from the subclavian artery. The increase of the coronary blood flow observed after occlusion was shown to depend strictly on its duration. Deendothelization of coronary vessels decreased the RH significantly. In coronary bed the infusion of L-arginine was accompanied by an increase of RH and endothelium-dependent acetylcholine-induced vasodilation. L-arginine produced its effect only when the endothelium was intact, whereas NO synthase inhibition substantially decreased the RH and vasodilating response to intracoronary administration of acetylcholine. It was concluded that the RH was endothelium-dependent and that nitric oxide of endothelial origin was the active humoral component of this reaction.

[The role of nitric oxide in the development of reactive hyperemia in the coronary bed]. / Rol' okisi azota v razvitii reaktivnoi giperemii v koronarnom rusle.

De-endothelialization of the coronary vessels induced a 3-4-fold decrease in the level of hyperemia in anesthetised dogs. Infusion of L-arginine augmented the reactive hyperemia and the endothelium-dependent relaxation in response to acetylcholine administration. The reactive hyperemia seems to be wholly depending on the endothelium, being conditioned by the effect of endothelium-derived nitric oxide.

Involvement of endothelium in vasodilating effects of vintoperol.

Experiments were performed on vessels of the femoral vascular bed of anesthetized dogs and on isolated rings of the rat pulmonary artery, vena cava, and thoracic aorta. Vintoperol was administered intra-arterially (0.01, 0.1, and 0.3 mg/kg/min for 10 min) or added in vitro (10(-4) M). De-endothelialization by saponin (0.5 mg/ml for 5 min) of intact vascular beds or mechanical endothelium removal in rings decreased vasodilation or relaxation by 50-60% vs. control. In de-endothelialized vascular beds, vintoperol (0.3 mg/kg/min) increased blood flow by 18 +/- 5% but 47 +/- 4% under control conditions (p < 0.05). Methylene blue (10 mg/kg) reduced the increment of blood flow to vintoperol from 47 +/- 4 to 24 +/- 4% (p < 0.05). After de-endothelialization of the isolated pulmonary artery, relaxation of precontracted segments was reduced (21 +/- 4% vs. 56 +/- 5% under control conditions; p < 0.05). Vintoperol-induced relaxation of vascular rings was also inhibited by gossypol (2 x 10(-5) M) or methylene blue (5 x 10(-5) M); the level of inhibition (50-100%) or methylene blue (5 x 10(-5) M); the level of inhibition (50-100%) depended on the duration of exposure to the inhibitors. In conclusion, relaxation to vintoperol must be mediated by the release of endothelium-derived nitric oxide.

On the mechanism of the involvement of endothelium in reactive hyperemia.

Experiments on anesthetized dogs and on vascular test-preparations demonstrated that reactive hyperemia (RH) was accompanied by the appearance of vasodilator in the blood, and that the level increased with the duration of occlusion of the artery. Removal of the endothelium of the part of the vascular bed studied using saponin, decreased the RH and relaxation of a test-preparation. A rise of pressure in the vascular bed, and a decrease in the deformability of the endothelium resulting from pretreatment with dimerized glutaraldehyde, affected both the hyperemia and the reaction of the vascular preparation in a similar way. It was concluded that the RH resulted from the secretion of vasoactive substances by the endothelium in response to a fall in intravascular pressure.

[The participation of humoral factors released by the endothelium in the development of reactive hyperemia]. / Uchastie gumoral'nykh faktorov, vydeliaemykh éndoteliem, v razvitii reaktivnoi giperemii.

In anesthetized dogs and on test-preparations of isolated vascular rings of femoral artery used for detection of appearance of vasoactive substances in venous blood, the reactive hyperemia was accompanied by the appearance of vasodilation substances in blood, the concentration of which increased with the occlusion duration. Chemical injury of endothelium by saponin, inhibition of lipoxygenase by quercetin and guanylate cyclase by methylene blue decreased the reactive hyperemia and the relaxation of test-preparation. Cyclooxygenase inhibition by indomethacin did not affect the reactive hyperemia or release of vasoactive substances. The endothelium seems to play an important role in development of reactive hyperemia induced by endothelium-derived relaxing factor release.

[Mechanisms involving the endothelium in reaction of reactive hyperemia]. / O mekhanizmakh vovlecheniia éndoteliia v reaktsiiu reaktivnoi giperemii.

The experiments on anesthetized dogs and on test-preparations of isolated vascular rings of femoral artery used for detection of appearance of vasoactive substances in venous blood demonstrated that the response of reactive hyperemia is accompanied by the appearance of vasodilation substances in the blood, the concentration of which taking into account the reaction of relaxation of vascular preparation, increases with the occlusion duration. Chemical inhibition of endothelium of a studied bed by saponin essentially decreases the reactive hyperemia and relaxation of test-preparation. The rise of pressure in an overlapped part of a bed and the decrease in the deformation of endothelium with the help of dimerized glutaraldehyde treatment affected the hyperemia and vascular preparation reaction in the similar way. We concluded that the reaction of reactive hyperemia is the result of the vasoactive substances secretion by endothelium in response to a decrease in intravascular pressure.

[Role of the endothelium in the development of reactive hyperemia]. / Rol' éndoteliia v razvitii reaktivnoi giperemii.

The experiments on anesthetized dogs demonstrated that reaction of the femoral vessels reactive hyperemia essentially decreased after chemical inhibition of endothelium by saponin, inhibition of lipoxygenase by quercetin and guanylate cyclase by methylene blue. Reaction was increased after cyclooxygenase inhibition by indomethacin. We concluded that the endothelium plays an important role in reaction of reactive hyperemia by endothelium-derived relaxing factor release.