ABSTRACT
The influence of chronic stress (footshock combined with randomized light flashes) on acute stress-induced (immobilization) release of noradrenaline, dopamine and serotonin in rat lateral hypothalamus was assessed by microdialysis. The chronic stress resulted in an increase and prolongation of the acute stress-induced release of noradrenaline but not of dopamine and serotonin. The increased rate of accumulation of dioxyphenylacetic acid and unchanged accumulation of homovanillic acid (dopamine metabolites) and dopamine during and after the acute stress in chronically stressed animals reflect a rise of synthetic activity of catecholaminergic systems in response to acute stress and reuptake increase. Marked stress-induced increase in hydroxyindoleacetic acid in chronically stressed rats without any changes in the ST dynamics may be regarded in a similar way. A significant increase in potassium-stimulated release of all the studied monoamines was found while their basal level remained unchanged. The conclusions was made that the hyperergic release of neurotransmitters may be the basis of an inadequate response of animals to acute stress, i.e., one of the neurotic symptoms.
Subject(s)
Biogenic Monoamines/physiology , Hypothalamus/physiopathology , Stress, Physiological/physiopathology , Acute Disease , Analysis of Variance , Animals , Biogenic Monoamines/analysis , Chromatography, High Pressure Liquid , Chronic Disease , Male , Microdialysis/methods , Microdialysis/statistics & numerical data , Physical Stimulation/methods , Rats , Rats, Wistar , Restraint, PhysicalABSTRACT
A mathematic model depicting the interaction of glucocorticoids with the target cell is proposed. Specific features of cortisol and dexamethasone distributions in thymocytes in a wide range of hormonal concentrations have been analyzed. It has been established that specific action of glucocorticoids is dependent on the binding affinity and the number of the binding sites of hormones in the topographically different cell receptor systems (intracellular and membrane glucocorticoid receptors).
Subject(s)
Glucocorticoids/pharmacokinetics , Models, Biological , Thymus Gland/metabolism , Animals , Cell Membrane/metabolism , Cytosol/metabolism , Dexamethasone/pharmacokinetics , Dose-Response Relationship, Drug , Hydrocortisone/pharmacokinetics , Male , Mathematics , Rats , Receptors, Glucocorticoid/metabolism , Thymus Gland/cytology , TritiumABSTRACT
The phenomenon of precipitation in protein solutions after addition of hepatotropic diagnostic media is described. The examination of different proteins and media allows the coagulative mechanism to be proposed, through which the electrostatic interactions between di- and polyvalent ligands with positively charged protein groups play the major role. It is suggested that the described phenomenon contributes to the nephrotoxicity of some drug groups.
Subject(s)
Hemoglobins/drug effects , Liver/drug effects , Serum Albumin, Bovine/drug effects , Serum Albumin/drug effects , Animals , Cattle , Chemical Precipitation , Diatrizoate Meglumine/pharmacology , Drug Interactions , Hemoglobins/metabolism , Humans , Hydrogen-Ion Concentration , In Vitro Techniques , Iodamide/pharmacology , Iodipamide/pharmacology , Protamines/pharmacology , Protein Binding/drug effects , Rats , Serum Albumin/metabolism , Serum Albumin, Bovine/metabolism , Sulfobromophthalein/pharmacologyABSTRACT
The authors suggest the construction of a cannula for microdialysis combined with a light guide of a laser doppler flowmeter. Such a design allows monitoring of blood flow intensity in the environment of the microdialyzer. An advantage of local administration of vasoactive agents is that they cause no effect on systemic arterial pressure. When administered locally, sodium nitroprusside increased whereas the inhibitor NO-synthase reduced blood flow intensity. No changes were detected in the local blood flow in administration of phenylephrine and nitroglycerin through the dialyzer. Tetrodoxin insignificantly reduced the blood flow. The existence of a diffusion barrier for some agents as well as the long period of time needed for attaining the state of equilibrium after beginning perfusion of the solution containing the agent under test is among the disadvantages of local administration.
Subject(s)
Cerebrovascular Circulation/drug effects , Microdialysis/methods , Vasoconstrictor Agents/administration & dosage , Vasodilator Agents/administration & dosage , Animals , Enzyme Inhibitors/administration & dosage , Laser-Doppler Flowmetry/instrumentation , Laser-Doppler Flowmetry/methods , Male , Microdialysis/instrumentation , NG-Nitroarginine Methyl Ester/administration & dosage , Nitric Oxide Synthase/antagonists & inhibitors , Nitroglycerin/administration & dosage , Nitroprusside/administration & dosage , Phenylephrine/administration & dosage , Rats , Rats, Wistar , Tetrodotoxin/administration & dosageABSTRACT
Dynamics of the transcapillary turnover of liquids in the brain and soft tissues of the head was studied in pre-trained small laboratory animals (rats) during antiorthostasis, and their controls. Training for antiorthostasis consisted of tail-suspension for 2 hours in the period of two weeks. The transcapillary turnover of liquids was determined based on the arteriovenous difference in blood density (AVBD). Blood density was measured with the equipment of Anton Paar K.G. (Austria). Rats in the horizontal position did not exhibit any apparent trend in the dynamics of blood transcapillary turnover. Blood drain from the interstitial space at the time of return of the antiorthostatic rats into the horizontal position was dependent on the length of antiorthostatis. Beginning from the fifth hour of tail suspension, changed AVBD sign was an indication of edema of the muzzle soft tissue. This phenomenon was not observed in the pre-trained rats. Similar results were obtained in the investigation of cerebral vessels AVBD. Hence, changes in the transcapillary turnover of liquids in cranium during antiorthostatic hypokinesia point to the dominance of liquid filtration into the extravascular space. Antiorthostatic pre-training precludes liquid deposition in the interstitial space of the brain and the cerebral soft tissue.
Subject(s)
Body Fluids/metabolism , Brain/metabolism , Cerebrovascular Circulation/physiology , Extracellular Space/metabolism , Hypokinesia/physiopathology , Hypotension, Orthostatic/rehabilitation , Animals , Brain/blood supply , Capillaries/metabolism , Disease Models, Animal , Follow-Up Studies , Hindlimb Suspension , Hypotension, Orthostatic/physiopathology , Male , Physical Conditioning, Animal/methods , Rats , Rats, WistarABSTRACT
The nitrogen oxide NO-dependent regulation of the cerebral blood flow was studied before and after 24-hr head-down immobilization (HDI) of intact and pre-trained rats. Training consisted in 2-hr tail-suspension each day of the 2-wk period. Blood flow was determined with the laser Doppler flowmetry following local injection of a NO synthesis blocker (L-NAME), and NO (sodium nitroprusside). Neither HDI nor pre-training per se influenced NO tonic production in the cortex of large hemispheres and cerebellum. However, in pre-trained animals HDI resulted in a significant blood flow response to the local blockade of NO synthesis in the cerebellum. None of the animals changed the reaction of the blood flow to the local injection of sodium nitroprusside. The conclusion was drawn that alteration in the NO-dependent regulation of the brain blood flow in pre-trained animals could manifest of adaptation to HDI in the course of 24-hr suspension.
Subject(s)
Adaptation, Physiological , Cerebrovascular Circulation/physiology , Nitric Oxide/physiology , Weightlessness Simulation , Adaptation, Physiological/drug effects , Animals , Cerebrovascular Circulation/drug effects , Enzyme Inhibitors/pharmacology , Head-Down Tilt/physiology , Laser-Doppler Flowmetry , Male , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Donors/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitroprusside/pharmacology , Random Allocation , Rats , Rats, Wistar , Time FactorsSubject(s)
Excitatory Amino Acids/physiology , Hypothalamus/physiopathology , Neurotransmitter Agents/physiology , Stress, Physiological/physiopathology , Adaptation, Physiological , Animals , Asparagine/analogs & derivatives , Asparagine/chemistry , Asparagine/pharmacology , Aspartic Acid/analogs & derivatives , Aspartic Acid/pharmacology , Hypothalamus/drug effects , Male , Microdialysis , Rats , Rats, WistarABSTRACT
The activity of noradrenergic system of lateral hypothalamus and hemodynamics were studied during acute restraint in chronically stressed and control rats. Arterial blood pressure in rest was negatively proportional to basal norepinephrine concentration in dialysate of lateral hypothalamus. Animals with high increase of norepinephrine levels in dialysate during acute stress had rapid return of arterial blood pressure to basal values while stress-induced hypertension in the beginning of restraint was the same as in rats with low increase of norepinephrine levels. Data obtained show the depressor role of noradrenergic system of lateral hypothalamus. The enhanced reactivity of noradrenergic depressor system may be one of the mechanisms providing cardiovascular adaptation to stress.
Subject(s)
Stress, Physiological/physiopathology , Adaptation, Physiological , Animals , Blood Pressure , Chronic Disease , Heart Rate , Hypothalamus/metabolism , Male , Microdialysis , Norepinephrine/metabolism , Rats , Rats, Wistar , Stress, Physiological/metabolismABSTRACT
Physostigmine and an 1-hour immobilisation stress similarly affected functions of the sympatho-adrenal and cardiovascular systems activating the catecholamine secretion and increasing the blood pressure. Yohimbine potentiated the secretory effect but did not change the pressor effect. Intermediate administration of atropine completely eliminated both effects of physostigmine but, being administered prior to the immobilisation, it potentiated the secretory response without affecting the pressor response. The findings reveal a difference in central cholinergic mechanisms of neurohumoral and haemodynamic responses to physostigmine and stress.