ABSTRACT
The article continues the series of our publications on the problem of nitric oxide (NO) and its cyclic conversion in mammals. This review is held to analysis of nitric oxide role in regulation of cardiovascular system and in alocation of NO-synthases in myocardium. Molecular, biochemical and cytophysiological aspects that linked, with spatial localization of NO-synthases and mechanisms of NO content regulation in myocardium are considered. The results of author's investigations along the cyclic convertion of NO and literature data about compartmentalization of NO-synthases in myocardium are included in this paper. The contradictory and dissimilar facts about regulatory and toxic role of nitric oxide in cardiovascular system are represented.
Subject(s)
Myocardium/metabolism , Nitric Oxide/metabolism , Animals , Arrhythmias, Cardiac/metabolism , Arrhythmias, Cardiac/physiopathology , Calcium/physiology , Cardiomyopathy, Dilated/metabolism , Cardiomyopathy, Dilated/physiopathology , Cardiovascular System/metabolism , Humans , Myocytes, Cardiac/metabolism , Nitric Oxide Synthase/metabolismABSTRACT
Investigations with Macaca mulatta of 4-5 yrs. of age with the body mass of 4.5-6.5 kg showed that 10 days of tilting with the head end at .5 degrees reduced body temperature but not levels of interleukine-1beta and interleukine-6 in blood plasma. On the next days after return of animals to cages IL-6 was found to increase sharply in more than 10 times. On subsequent 4 days both IL -1beta and IL-6 were within the normal range.
Subject(s)
Hypokinesia/blood , Interleukin-1beta/blood , Interleukin-6/blood , Animals , Macaca mulattaABSTRACT
In acute experiments on rats, systemic inflammation was induced by intraperitoneal E. coli lipopolysaccharide (LPS) injection that in a dose of 5 microg/kg caused an increase in rectal temperature by 1.0 +/- 0.3 degrees C and 2.5 +/- 0.2 degrees C, respectively, at thermobox temperature of 22 degrees C and 35 degrees C, and in a dose of 1000 microg/kg caused its decrease by 1.7 +/- 0.6 degrees C at 22 degrees C and increase by 0.4 +/- 0.1 degrees C at 35 degrees C. In all the animals, cardiomyocytes demonstrated a functional tension which appeared as a growing number of mitochondria, nuclear pores and cisterns of the endoplasmic reticulum. In the microvessels, when both LPS doses were administered, leukocyte and macrophage adhesion to endotheliocyte membrane was demonstrated. After LPS injection in a dose of 1000 microg/kg, numerous large secretory granules were observed under the sarcolemma close to the microvessels in hormone-producing cardiomyocytes, containing natriuretic hormone. Contractile cardiomyocytes showed signs of early-stage apoptosis (accumulation of small mitochondria with electrone dense matrix, cytoplasmic invagination into the nucleus, formation of apoptotic bodies). LPS in a dose of 1000 microg/kg at thermobox temperature of 35 degrees C induced changes in some cardiomyocytes with the signs of late-stage apoptosis (condensed nucleus and cytoplasm).
Subject(s)
Escherichia coli , Lipopolysaccharides/pharmacology , Myocardium/ultrastructure , Systemic Inflammatory Response Syndrome/pathology , Animals , Apoptosis , Body Temperature , Cell Adhesion , Endothelial Cells/physiology , Endothelium, Vascular/ultrastructure , Heart Atria/ultrastructure , Leukocytes/physiology , Macrophages/physiology , Male , Microcirculation/ultrastructure , Myocytes, Cardiac/ultrastructure , Rats , Rats, WistarSubject(s)
Gram-Negative Bacteria , Lipopolysaccharides/toxicity , Lung/innervation , Nerve Fibers/drug effects , Vagus Nerve/drug effects , Afferent Pathways/drug effects , Animals , Male , Rats , Rats, Inbred Strains , Respiration/drug effects , Respiration Disorders/microbiology , Vagus Nerve/cytologyABSTRACT
In experiments on rats, changes of the ultrastructure of myocardial histo-hematic barriers in the right atrium during short-term and prolonged heat stress were studied. Short-term heat exposure (40 degrees C, 30 and 60 min) increased the rectal temperature by 3.0-3.5 degrees C. Immediately after heat exposure and 24 and 48 h following the exposure, the destructive and compensatory adaptive alterations in the microcirculatory bed were detected, accompanied by an edema of the pericapillary space and the changes in the size of mitochondria under the cardiomyocyte sarcolemma. Prolonged heating (40 degrees C, 4 h daily for 28 days) led to an increase in the rectal temperature by 0.4-1.6 degrees C. Changes in the microcirculatory bed had both dystrophic and compensatory adaptive nature. Erythrocyte and thrombocyte sludge and erythrocyte lysis were found in the lumen of microvessels. The number of endocytotic vesicles in endotheliocytes was variable; endotheliocyte nuclei had increased electron density and irregular outline. Myelin-like structures and apoptotic bodies were found in the pericapillary spaces. Under the cardiomyocyte sarcolemma the accumulation of mitochondria and sarcoplasmic vacuolization were noted. Comparison of short- and long-term effects of heat on histohematic barriers in the right atrium shows more significant changes after prolonged heat stress.
Subject(s)
Heat Stress Disorders/pathology , Heat-Shock Response , Myocardium/ultrastructure , Myocytes, Cardiac/ultrastructure , Animals , Body Temperature Regulation , Heart Atria/ultrastructure , Male , Microcirculation/ultrastructure , Microscopy, Electron, Transmission , Rats , Rats, Wistar , Sarcolemma/ultrastructure , Time FactorsABSTRACT
In acute experiments performed on rats placed in heat-chamber (40 degrees C, 30- and 60-minutes-long exposure), an increase in NADPH-diaphorase (NADPH-d) and succinate dehydrogenase (SDH) activities were found in the neurons of intramural ganglia of the right atrium, while SDH and lactate dehydrogenase (LDH) activities were increased in cardiomyocytes. Hormone-producing cardiomyocytes, containing atrial natriuretic peptide, had numerous large secretory granules under the sarcolemma close to the microvessels. In contractile cardiomyocytes, the signs of early stage of apoptosis were observed including the subsarcolemmal accumulation of small mitochondria and cytoplasmic invaginations into the nucleus. Prolonged heating (37 degrees C, 4 h daily) led to an increased activities of NADPH-d and SDH in neurons of intramural ganglia of the right atrium and of NADPH-d and LDH in cardiomyocytes. Secretory granules in hormone-producing cardiomyocytes were small and reduced in number. Cardiomyocytes showing the signs of the late stage of apoptosis (with nuclear and cytoplasmic condensation) were demonstrated.
Subject(s)
Heat-Shock Response , Myocardium/pathology , Myocytes, Cardiac/ultrastructure , Neurons/ultrastructure , Animals , Apoptosis , Ganglia, Autonomic/enzymology , Heart Atria/innervation , Heart Atria/metabolism , Heart Atria/pathology , L-Lactate Dehydrogenase/metabolism , Male , Microscopy, Electron, Transmission , Mitochondria, Heart/ultrastructure , Myocardium/enzymology , Myocytes, Cardiac/enzymology , NADPH Dehydrogenase/metabolism , Neurons/enzymology , Rats , Rats, Wistar , Sarcolemma/ultrastructure , Secretory Vesicles/ultrastructure , Succinate Dehydrogenase/metabolism , Time FactorsABSTRACT
Experiments were performed on white male Wistar rats under Nembutal-urethane anesthesia. Transient ischemia (10 min) was produced by clamping of the carotid arteries. Some neurons in the parietal area of the cerebral cortex and endotheliocytes in blood vessels showed increases in NO synthesis and in the activity of energy metabolism enzymes (SDH, LDH). Changes in the ultrastructure of some neurons and synaptic formations provided evidence of a state of functional pressure, while changes in others indicated irreversible changes (disturbances in lipid metabolism and destructive changes in the nucleus and cytoplasm).
Subject(s)
Cerebral Cortex/ultrastructure , Ischemic Attack, Transient/enzymology , Neurons , Nitric Oxide Synthase/metabolism , Animals , Disease Models, Animal , Ischemic Attack, Transient/metabolism , Ischemic Attack, Transient/pathology , Lactate Dehydrogenases/metabolism , Male , Microscopy, Electron, Transmission/methods , Neurons/enzymology , Neurons/ultrastructure , Rats , Rats, Wistar , Succinate Dehydrogenase/metabolismABSTRACT
Experiments were performed on male Wistar rats under nembutal-urethan anesthesia. Short-time (10 min) cerebral ischemia was induced by bilateral ligation of carotid arteries. This was followed by an increased synthesis of NO and activity of energy metabolism enzymes (SDH, LDH) in a part of neurons of the parietal cortex and in endotheliocytes of blood vessels. The ultrastructural changes of some neurons and synaptic formations indicated functional tension, while in the others the irreversible changes (disturbed lipid metabolism, destructive alterations of the nucleus and cytoplasm) were found.
Subject(s)
Brain Ischemia/pathology , Energy Metabolism , Neurons , Nitric Oxide Synthase/metabolism , Parietal Lobe , Animals , Brain Ischemia/enzymology , Brain Ischemia/metabolism , Disease Models, Animal , L-Lactate Dehydrogenase/metabolism , Male , Microscopy, Electron , NADPH Dehydrogenase/metabolism , Neurons/enzymology , Neurons/metabolism , Neurons/ultrastructure , Parietal Lobe/enzymology , Parietal Lobe/metabolism , Parietal Lobe/ultrastructure , Rats , Rats, Wistar , Succinate Dehydrogenase/metabolism , Time FactorsABSTRACT
The aim of the present work was to identify the role of ATP acting on specific P2X receptors in the central mechanisms of thermoregulation. Immunohistochemical studies demonstrated that brainstem structures involved in controlling body temperature contained large number of nerve cells bearing P2X ATP receptors. Experiments on conscious rats involving intracerebroventricular administration of an ATP analog and P2X antagonists showed that both activation and blockade of central P2X receptors produced marked changes in body temperature. Analysis of the effects of these substances provided grounds for suggesting that ATP acting on P2X receptors fulfils an important function in the mechanisms of transmitting afferent information from peripheral thermal receptors to thermoregulatory centers in the brainstem with responsibility for heat loss, while in pyrogen-induced fever ATP acting on these receptors may be involved in the activity of the endogenous antipyretic system.
Subject(s)
Adenosine Triphosphate/physiology , Body Temperature Regulation/physiology , Receptors, Purinergic P2/physiology , Adaptation, Physiological , Adenosine Triphosphate/analogs & derivatives , Adenosine Triphosphate/pharmacology , Animals , Body Temperature Regulation/drug effects , Endotoxins/pharmacology , Fever/physiopathology , Hypothalamus/cytology , Immunohistochemistry , Male , Medulla Oblongata/cytology , Medulla Oblongata/physiology , Neurons, Afferent/physiology , Purinergic P2 Receptor Agonists , Purinergic P2 Receptor Antagonists , Rats , Rats, Sprague-Dawley , Rats, Wistar , TemperatureABSTRACT
The aim of the present study was to elucidate the role of extracellular ATP acting on specific P2X receptors in the central mechanisms of thermoregulation. Using immunohistochemistry methods, it was found that the brainstem structures involved in the body temperature regulation contain a large number of nerve cells which possess P2X receptors for ATP. Experiments with intracerebroventricular application of a stable ATP analogue and P2X receptor antagonists to conscious rats showed that both activation and blockade of central P2X receptors resulted in marked changes in body temperature. Analysis of the effects of these agents suggests that ATP by acting on P2X receptors performs an important function in the mechanisms of transmission of afferent information coming from peripheral thermoreceptors to the brainstem thermoregulatory centres responsible for heat loss, and during pyrogen-induced fever can be involved in the action of the endogenous antipyretic system.
Subject(s)
Adenosine Triphosphate/physiology , Body Temperature Regulation/physiology , Neurons, Afferent/physiology , Receptors, Purinergic P2/physiology , Adenosine Triphosphate/analogs & derivatives , Adenosine Triphosphate/pharmacology , Animals , Body Temperature Regulation/drug effects , Hypothalamus/cytology , Immunohistochemistry , Male , Medulla Oblongata/cytology , Purinergic P2 Receptor Agonists , Purinergic P2 Receptor Antagonists , Rats , Rats, Sprague-Dawley , Rats, Wistar , Receptors, Purinergic P2X , Receptors, Purinergic P2X2 , Stress, Physiological/physiopathology , Suramin/pharmacology , TemperatureABSTRACT
In anaesthetised rats, i.p. administration of the Echerichia coli lipopolysaccharide in doses 5 mcg/kg (LPS) increased afferent activity of the cervical vagus, whereas 100 and 1000 mcg/kg doses inhibited the afferent discharges. Pyrogen-free saline (PFS) did not alter the activity. Rectal temperature (RT) was decreased by the PFS and by large doses of the LPS. Sodium salicylate administration prevented the effects.
Subject(s)
Afferent Pathways/drug effects , Body Temperature/drug effects , Escherichia coli , Lipopolysaccharides/pharmacology , Neuroimmunomodulation , Vagus Nerve/drug effects , Afferent Pathways/physiology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Male , Rats , Rats, Wistar , Sodium Salicylate/pharmacology , Vagus Nerve/physiologyABSTRACT
The paper presents the results of examination of the mechanisms of development of different physiological dysfunctions (diminished cardiac electrical stability, fibrillation threshold fall) under emotional stress. Search was made for their drug correction (nitric oxide precursor L-arginine, the NO synthase blocker Ng-methyl-L-arginine and sodium nitrate). Experiments have indicated that L-arginine and sodium nitrate restore cardiac electrical stability. The normalizing effects of NO donors depended on the stage of cardiac disorders.
Subject(s)
Cardiovascular Physiological Phenomena , Nitric Oxide/physiology , Stress, Psychological/etiology , Acute Disease , Animals , Cardiovascular Physiological Phenomena/drug effects , Chronic Disease , Disease Models, Animal , Hemodynamics/drug effects , Male , Nitric Oxide Donors/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Rats , Rats, Wistar , Stress, Psychological/physiopathologyABSTRACT
The authors make an attempt to substantiate the idea that proteinase inhibitors can produce a noticeable effect on the integration of functions. It is suggested that proteinase inhibitors play a special role in providing coupling between the body's functional systems in the conditions that may disturb the structural and functional integrity of the organism. They paper provides experimental evidence for the effect of the serine proteinase inhibitor alpha 1-antitrypsin on the thermal regulatory system and couples functional systems that provide behavioral responses. Possible mechanisms of systemic action of proteinase inhibitors and their involvement in the integrative activity of the nervous system are discussed.
Subject(s)
Adaptation, Physiological/drug effects , Central Nervous System/physiology , Human Activities , Serine Proteinase Inhibitors/pharmacology , alpha 1-Antitrypsin/pharmacology , Adaptation, Physiological/physiology , Animals , Body Temperature/drug effects , Central Nervous System/drug effects , Central Nervous System/enzymology , Endopeptidases/drug effects , Endopeptidases/metabolism , HumansSubject(s)
Electrophysiology/instrumentation , Microelectrodes , Animals , Equipment Design , Glass , Interneurons/physiology , LymnaeaABSTRACT
Alterations caused by hypothermal stress in neurons of pelvic plexus in rats were studied histochemically. The increase of catecholamine content in neurons and serotonin--in small intensely fluorescent cells (SIFC), suppression of acetyl cholinesterase activity in neurons were demonstrated after the short-term hypothermal stress leading to moderate hypothermia. Cooling of rats following the preliminary section of pelvic nerves does not prevent the above mentioned changes in neurons and SIFC. The participant of adrenergic nerves and SIFC in peripheral mechanisms of thermoregulation is under discussion.
Subject(s)
Body Temperature Regulation/physiology , Cold Temperature , Energy Metabolism/physiology , Hypogastric Plexus/pathology , Stress, Physiological/pathology , Animals , Catecholamines/metabolism , Fluorescence , Histocytochemistry , Hypogastric Plexus/metabolism , Neurons/metabolism , Rats , Rats, Wistar , Serotonin/metabolismABSTRACT
Reactive changes of structural and functional organization of pre- and paravertebral sympathetic ganglia were studied in experimental fever and under the effect of high temperatures using electron microscopy and histochemical methods. Changes in histochemical and ultramicroscopic characteristics of neuroglial complex, synaptic apparatus and of histohematic barrier were demonstrated. Correlation between those changes and the dose and duration of the challenge was established.
Subject(s)
Ganglia, Sympathetic/drug effects , Heating , Lipopolysaccharides/pharmacology , Pyrogens/pharmacology , Animals , Catecholamines/metabolism , Cats , Fever/chemically induced , Fever/pathology , Fluorescence , Ganglia, Sympathetic/metabolism , Ganglia, Sympathetic/ultrastructure , Guinea Pigs , Histocytochemistry , Mesentery/innervation , Microscopy, Electron , Neuroglia/drug effects , Neuroglia/ultrastructure , Synapses/drug effects , Synapses/ultrastructureABSTRACT
Many years' experience with complex supervision of the environmental radiation situation, the specific features of the population's physiological and health status after radiation accidents (the Chernobyl, Kyshtym and other accidents). The paper emphasized the necessity of having a knowledge of the specific features of the influence of a radiation factor (and its components) on establishing the radiation dose for the population due to the environmental peculiarities of the radiation background in different regions and abnormal zones of the Earth. The paper provides evidence for the need to apply an environmental and physiological approach to working out the standards of radiation doses for the inhabitants of post-accident polluted areas. To this end, a concept of the regional standard of exposure is proposed for different regions of the Earth with regard to the specific natural radiation background, technogenic and medical "additives" on making diagnostic and therapeutical efforts by using X-rays and radiation therapy. A new concept is offered to develop the life-support systems in the areas exposed to radiation contamination, whose main goal is to minimize radiation exposures with regard of data on each area-specific data on the regional standard of the pre-accident radiation background, technogenic background, medical additives and prediction of future radiation doses. Exposure of the population to radiation is minimized by reasonably operating its components and making special life regimens in the contaminated areas.