Dose-rate dependent effects of ionizing radiation on vascular reactivity.

This study was designed to investigate the dose-rate dependent effects of ionising radiation on endothelium- and NO-mediated reactivity of aorta and coronary vessels. Rats were exposed to acute ((137)Cs, 9 x 10(-4) Gy s(-1), 18 min) and chronic ((137)Cs, 2.8 x 10(-7) Gy s(-1), 41 days) radiation in 1 Gy dose. Acute irradiation transiently increased coronary flow in eNOS-activity-dependent manner on day 3 after exposure. In striking contrast, chronic irradiation caused a significant depression of coronary flow even on day 90 after irradiation and abolished the effects of NO-synthase inhibitor N-nitro-L-arginine methyl ester (10 micromol l(-1)). Furthermore, low intensity radiation strongly diminished the vasodilator properties of NO-donor sodium nitroprusside (5 micromol l(-1)). A similar pattern was observed in aortic rings. Endothelium-dependent vasodilation was increased on days 3 and 10 after acute irradiation, but strongly inhibited following chronic exposure for the entire post-radiation period. This was accompanied by a diminished vasodilator response to NO-donor on days 3, 10 and 30 of post-radiation but not on day 90. The data suggest that ionising radiation in 1 Gy induces changes of aortic and coronary vessels reactivity depending on the dose-rate and the interval after exposure.

The effects of acute and chronic radiation on endothelium- and no-dependent vascular reactivity.

Endothelium- and NO-dependent relaxation of aortic segments and basal coronary flow and response of coronary vessels to exogenous NO in the Langendorff-perfused rat hearts were examined on the 3rd, 10th, 30th and 90th days following whole body irradiation in 1 Gy dose with different dose rate. NO-mediated elevation of coronary flow and increased aortic endothelium-dependent vasodilation were found at the early stage after acute irradiation (137Cs, 9 x 10(-4) Gy/s), while vascular reactivity to exogenous NO was not changed. Chronic irradiation (137Cs, 2.3 x 10(-7) Gy/s) significantly impaired endothelium-dependent relaxation within whole experimental period and decreased NO component of basal coronary flow at the 3rd, 10th and 90th day. It was associated with attenuated reactivity to NO-donor in aorta one month after irradiation and in the coronary vessels--shortly after irradiation. In the delayed period endothelial dysfunction and the diminution of NO-dependent coronary flow were mediated by selective impairment of NO synthesis/release. Decreased survival rate of the lethally-irradiated Nwnitro-L-arginine methyl ester-treated animals revealed radiosensitizing properties of NO synthase inhibition. The data obtained indicate the involvement of NO in the alterations of vascular reactivity depending on the dose rate and on the interval after the irradiation.

[Role of NO-mediated mechanisms in post-irradiation changes of neurohormonal regulation of the heart function]. / Rol' NO-oposredovannykh mekhanizmov v postradiatsionnykh izmeneniiakh neirogormonal'noi reguliatsii funktsii serdtsa.

Investigations on isolated Langendorff-perfused rat heart have shown that after the impact of ionizing radiation in 1 Gy dose the myocardial contractility and relaxation are decreased. The inhibition of NO synthesis attenuates chrono- and inotropic responses of the heart and reaction of coronary vessels to norepinephrine (NE), increases negative inotropic and vasoconstrictor effects of carbamylcholine (CCh). In the irradiated animals the reaction of isolated heart to NE and CCh is decreased. The post-irradiation changes in adreno- and cholinoreactivity caused not only by changes in receptor sensitivity and density, but also by impairment of NO-mediated regulation of coronary flow and biomechanical heart function.

[Systemic approach to radiobiological studies]. / Sistemnyi podkhod v radiobiologicheskikh issledovaniiakh.

The principles of information theory were applied for analysis of radiobiological effects. The perception of ionizing radiations as a signal enables living organism to discern their benefits or harm, to react to absolute and relatively small deviations, to keep the logic and chronicle of events, to use the former experience for reacting in presence, to forecast consequences. The systemic analysis of organism's response to ionizing radiations allows explaining the peculiarities of effects of different absorbed doses, hormesis, apoptosis, remote consequences and other post-radiation effects.

[Age related features of postradiation changes of functional activity of local vascular renin-angiotensin system]. / Vozrastnye osobennosti postradiatsionnykh izmenenii funktsional'noi aktivnosti lokal'noi sosudistoi renin-angiotenzinovoi sistemy.

The postradiation changes of constriction effects of angiotensin II (Ang II) and angiotensin I (Ang I) on isolated preparations of thoracic aorta young and old rats which underwent gamma-irradiation in dose 1 Gy (137Cs, 9 x 10(-4) Gy/s) were investigated. It has been found, that the aging leads to the alteration of angiotensin receptors, which appears as changes in their density and/or sensitivity to action of agonist. With increase of age the activity of angiotensin-converting enzyme (ACE) in the wall of aorta is oppressed, and as a result, the level of local formation of Ang II and the constriction, caused by it are reduced. The inhibitory influence of endothelium on vasoconstriction effects of Ang II and Ang I in ontogenesis does not change. The influence of gamma-radiation in a dose of 1 Gy modifies the functional activity of the local vascular renin-angiotensin system (RAS): the sensitivity and/or density of angiotensin receptors and the activity of ACE increased the dilatation influences of endothelium were oppressed mainly for account of easing the synthesis of NO. The duration of postradiation infringements of functional activity of local vascular RAS in many respects are determined by the stage of ontogenic development of irradiated organism.

[Influence of hypoxia and anoxia on endothelium-dependent dilatation response of rat's aorta exposed to low-intensity gamma irradiation]. / Vliianie gipoksii i anoksii na éndotelii-zavisimye dilatatornye reaktsii aorty krys, podvergnutykh vozdeistviiu nizkointensivnykh gamma-izluchenii.

The study of isolated segments of aorta has shown that prolongated exposure of rats to gamma-radiation with 50 cGy dose (with a dose rate of 2.8 x 10(7) Gy/s) causes the decrease in endothelium-dependent dilatation responses to M-cholinoreceptors stimulation. During oxygenation the post-radiation changes are displayed within one month, and under functional loads, specifically, during perfusion by hypoxic and anoxic solutions--in more remote terms of the post-radiation period.

[Effect of prolonged gamma-irradiation on the functional state of heart and its adrenergic regulation at hypothyroidism]. / Osobennosti vliiania prolongirovannogo vozdeistviia gamma-izlucheniia na funktsional'noe sostoianie serdtsa i ego adrenergicheskuiu reguliatsiiu pri gipotireoze.

The study of heart isolated by Langendorf's method has shown that the prolongated gamma-irradiation of euthyroid rats in 1.0 Gy dose (2.8 x 10(-7) Gy/sec) causes the decrease in contraction ability, myocardium relaxation and functional response of heart to the stimulation of beta-adrenergic receptors, and the increase in myocardium reaction to the stimulation of alpha-adrenergic receptors. The irradiation of hypothyroid animals leads to more significant and long changes in contraction function of heart and its adrenergic regulation.

[The biomechanical function of the heart and its adrenergic regulation after long-term gamma radiation exposure]. / Biomekhanicheskaia funktsiia serdtsa i ee adrenergicheskaia reguliatsiia posle dlitel'nogo vozdeistviia gamma-izlucheniia.

The study of heart isolated by Langendorf's method has shown that the prolonged gamma irradiation of rats with 1.0 Gy dose (2.8 x 10(-7) Gy/sec) causes the decrease in contraction and relaxation ability, of myocardium, reduces functional response of heart to the stimulation of beta-adrenergic receptors, and increases of myocardium reaction to the stimulation of alpha-adrenergic receptors.

[The effect of stimulation of the adrenergic receptors on the frequency depression of the temporal parameters of the action potential in the right atrium of rats]. / Effekt stimuliatsii adrenergicheskikh retseptorov na chastotnuiu depressiiu vremennýkh parametrov potentsiala deistviia kardiomiotsitov pravogo predserdiia krys.

At a stimulation rate of 1 Hz, activation of alpha-adrenoreceptors prolonged the AP duration at 10%, 50%, and 90% repolarisation at 10(-7), 10(-6) M in the rat isolated right atria, but shortened it at a higher concentration of 10(-5) M. The frequency-induced depression of the AP duration became more evident in cardiomyocytes stimulated by 10(-7), 10(-6) M and less obvious at 10(-5) M of alpha-adrenoagonist. Activation of alpha-adrenoreceptors by isoprenalin shortened the AP duration and enhanced the stimulation-rate-dependent changes in the atrial AP configuration.

[The aspects of adenylate cyclase activity regulation in myocardium cell membranes during hypokinesia]. / Osobennosti reguliatsii aktivnosti adenilatsiklasy membran kletok miokarda pri gipokinezii.

Nonstimulated and isoproterenol, GTF, GITF, NaF stimulated activities of the adenylate cyclase in sarcolemma in white rats' myocardium was studied after two weeks of hypokinesia. As was established, in restrained animals the sensitivity of adenylate cyclase to the specified agents was increased and transition to the bimodal GTF regulation took place. It is hypothesised that involvement of membrane-bound Gi-proteins in the adrenergic effects on cardiomyocytes is one of mechanisms of the cardiotropic effects of restraint and heart distresses.

[Aorta dilatation after prolonged gamma-irradiation]. / Dilatatornye reaktsii aorty posle prolongirovannogo gamma-oblucheniia.

It is shown on isolated aorta preparations that prolonged gamma-irradiation of rats results in depression of endothelium-dependent and endothelium-independent vasodilatation responses to beta-adrenoceptors stimulation by isoprenaline and M-cholinoceptors by carbachol.

[Effects of prolonged gamma irradiation and hypoxia on bioelectrical activity of myocardial cells]. / Effekty prolongirovannogo gamma-oblucheniia i gipoksii na bioélektricheskuiu aktivnost' kletok miokarda.

It was established that prolonged gamma-irradiation of rats leads to the decrease of amplitude and duration of action potentials of right atrial cells, attenuation of the dependence of these electrophysiological characteristics upon the stimulation frequency, depression of the interval of cardiomyocytes reaction on the hypoxia. The revealed post-radiation changes determine the reduction of function resistance of heart cells bioelectrical activity and promote the initiation of arrhythmias.

[The contractile reactions of aortic segments to noradrenaline in the immediate and late postradiation periods]. / Sokratitel'nye reaktsii segmentov aorty na noradrenalin v blizhaishie i otdalennye sroki postradiatsionnogo perioda.

It is shown on isolated aorta preparations, that external gamma-irradiation of rats in dose 6 Gy results in intensification of endothelium-dependent relaxation which reaches of maximum in 30th days of post-radiation period. Constriction effect of norepinephrine on preparations without endothelium in remote terms after irradiation decreases with maximum on 90th days.

[The intensification of the vasodilator reactions of arterial vessels to stimulation of the beta-adrenergic receptors in the postradiation period]. / Usilenie vazodilatatornykh reaktsii arterial'nykh sosudov na stimuliatsiiu beta-adrenergicheskikh retseptorov v postradiatsionnyi period.

It was shown with endothelium-containing and endothelium-denuded aorta segments that external gamma-irradiation of rats (6.0 Gy) results in intensification of vasodilatation reactions on beta-adrenoceptor stimulation by isoprenaline with maximum in 30th day of post-radiation period. This post-radiation alteration is not related with endothelium-derived relaxing factor.

[Modifying effect of incorporated 137Cs on the mechanism of adrenergic control of myocardial contraction]. / Modifitsiruiushchee vliianie inkorporirovannogo 137Cs na mekhanizmy adrenergicheskogo kontrolia sokratitel'noi funktsii miokarda.

Incorporated 137Cs (absorbed dose of 0.26 Gy) causes decrease of myocardial's contractile function and inotropic response to beta-adrenagonists effect, isoproterenol-stimulated adenylate cyclase activity and beta-adrenoreceptors affinity. Adrenergic effects, mediated by alpha-adrenergic structures on heart contractile function, on the contrary, become stronger, that is due to the increase of the receptors' density on sarcolemma surface.

[Modification of adrenergic regulation of heart function under effect of radio-ecological factors within 10-kilometer zone of the accident at Chernobyl nuclear plant]. / Modifikatsiia adrenergicheskoi reguliatsii funktsii serdtsa pod vliianiem radioékologicheskikh uslovii v 10-kilometrovoi zone avarii na ChaES.

Rats kept within the ten-kilometer zone of Chernobyl disaster over a period of 30 days exhibited a decreased heart function response to beta-adrenoreceptor stimulus, reduced density of the receptor structures in cardiomyocytes and their affinity to specific agonists. The number of beta-adrenoreceptors in myocardium cells was restored in 6 months, but their affinity and heart function response to the effect of beta-adrenoagonists remained decreased. No significant changes were observed in regulation influenced indirectly via alpha-adrenoreceptors.

[Regulation of glucose transport in rat thymocytes after chronic gamma-irradiation]. / Reguliatsiia transporta glukozy v timotsitakh krys posle khronicheskogo g-oblucheniia.

Chronic gamma-irradiation (1 Gy, 100 mR/hr) increases cell titre in rat thymus and decreases glucose transport activation by phorbol ester. Animals kept in the Chernobyl evacuation zone over a period of 30 days exhibit reduced thymus cellularity and decreased PMA (200 nM) stimulation of glucose uptake by thymus cells.

[The effect of incorporated cesium-137 on the structure of the erythrocyte membranes]. / Vliianie inkorporirovannogo tseziia-137 na strukturnoe sostoianie mebran éritrotsitov.

The influence of incorporated cesium 137 (the absorbed doses of 0.26-0.08 Gy) on the erythrocyte membrane structure has been investigated. It has been shown that chronic internal exposure to gamma radiation causes structural reorganization of erythrocyte membranes at remote postirradiation times (in 3 and 6 months) that influences the annular membrane lipid.

[The adrenergic regulation of cardiomyocyte electrophysiological activity, cardiac biochemical function and coronary blood flow in rats with incorporated 131I]. / Adrenergicheskaia reguliatsiia élektrofiziologicheskoi aktivnosti kardiomiotsitov, biokhimicheskoi funktsii serdtsa i koronarnogo krovotoka u krys s inkorporirovannym 131I.

The study was made of the rat heart isolated according to Langendorf and right auricles. Intraperitoneal injections of 2.5 MBq/kg 131I were performed. Electrophysiological and biomechanical myocardium response to stimulation of alpha and beta-adrenoreceptors with isoprenalin and phenylephrine hydrochloride was analyzed. Postradiation modification of adrenergic control in animals with incorporated 131I appeared as reduced functional response of cardiomyocytes and intact heart to beta-adrenoagonist and enhanced response to alpha-agonist was detected.

[Adrenergic control of myocardial contractile function in rats with incorporated 137Cs]. / Adrenergicheskii kontrol' sokratitel'noi funktsii miokarda krys s inkorporirovannym 137Cs.

It was shown on isolated myocardium preparations that internal gamma irradiation of rats with 137Cs (1.6 MBq/kg) decreased the contractile function of ventricles and had no essential effect on the auricle contractility. The inotropic response of myocardium to activation of alpha-adrenergic receptors decreased, and of beta-adrenergic receptors decreased.