ABSTRACT
In rats with a hemodynamic disorder caused by acute myocardial ischemia, preliminary administration of beditin in a dose of 25 mg/kg fully prevents a manifold increase in the level of 45Ca2+ in the cytosol of brain cells and leads to enhanced trapping and accumulation of labeled calcium in endoplasmic reticulum. With respect to calcium binding in endoplasmic reticulum, the action of beditin substantially differs from that of verapamil.
Subject(s)
Adrenergic alpha-2 Receptor Antagonists , Anticonvulsants/therapeutic use , Brain/metabolism , Calcium Channel Blockers/therapeutic use , Calcium/metabolism , Dioxanes/therapeutic use , Seizures/drug therapy , Thiazoles/therapeutic use , Animals , Endoplasmic Reticulum/metabolism , Mice , Rats , Seizures/etiology , Seizures/metabolism , Species SpecificityABSTRACT
Beditin, or 2-(2-amino-4-thiazolyl)-1,4-benzodioxane hydrochloride, is a new benzodioxane derivative possessing antihypoxant and alpha 2-adrenoreceptor blocker properties. In contrast to idazoxan, a well-known alpha 2-adrenoreceptor blocker, beditin (3 mg/kg) significantly increases the circulation rate and decreases the blood vessel resistance in various brain structures of rats and cats without considerably changing their systemic hemodynamic indices. Upon a one-side ligation of the common carotid artery in rats, beditin prevented a sharp increase in the lactate dehydrogenase activity and a growth in the content of free ammonia in the brain, which are characteristic of the ischemic states. The ammonia-eliminating effect of beditin is related to an increase in the glutamate dehydrogenase activity in the reductive amination reaction.
Subject(s)
Adrenergic alpha-Antagonists/pharmacology , Brain/metabolism , Cerebrovascular Circulation/drug effects , Dioxanes/pharmacology , Receptors, Adrenergic, alpha-2/drug effects , Thiazoles/pharmacology , Animals , Blood Flow Velocity/drug effects , Brain/blood supply , Brain/enzymology , Cats , Glutamate Dehydrogenase/metabolism , Hypoxia/prevention & control , Hypoxia-Ischemia, Brain/metabolism , Hypoxia-Ischemia, Brain/physiopathology , Hypoxia-Ischemia, Brain/prevention & control , L-Lactate Dehydrogenase/metabolism , Male , Muscle, Skeletal/blood supply , Muscle, Skeletal/metabolism , Rats , Rats, Wistar , Skin/blood supply , Skin/metabolism , Vascular Resistance/drug effectsABSTRACT
Experiments on rats showed that the morpho-functional state of the cerebral cortex microcirculatory bed suffers marked changes in different periods of hypokinesia. This was accompanied with obvious morphological changes in the brain, the development of brain edema in particular. It was found that the GABAergic agents which we used ranked below Ca-antagonists in antiedemic activity.
Subject(s)
Brain/drug effects , Calcium Channel Blockers/pharmacology , Cerebrovascular Circulation/drug effects , GABA Agents/pharmacology , Animals , Bicuculline/pharmacology , Brain/pathology , Brain/physiopathology , Brain Edema/prevention & control , Dioxanes/pharmacology , Female , GABA Antagonists/pharmacology , GABA-A Receptor Antagonists , Male , Microcirculation/drug effects , Nifedipine/pharmacology , Piracetam/pharmacology , Rats , Rats, Wistar , Restraint, Physical , Thiazoles/pharmacology , Verapamil/pharmacology , gamma-Aminobutyric Acid/pharmacologyABSTRACT
In experiments on rats with acute myocardial infarction induced by occlusion of the left coronary artery in conscious animals the protective effect of verapamil on the heart, brain, liver, and kidneys in this disease was studied. The effectiveness of the drug was judged by the changes in the 45Ca2+ content in the intracellular structures (cytosol, mitochondria, endoplasmic reticulum) of the organs under study. A single injection of 200 micrograms/kg verapamil in acute myocardial infarction reduces considerably the content of 45Ca2+ in the intracellular structures of these organs and thus prevents the development of pathological processes.
Subject(s)
Calcium Channel Blockers/pharmacology , Calcium/metabolism , Cytosol/drug effects , Endoplasmic Reticulum/drug effects , Mitochondria/drug effects , Myocardial Ischemia/metabolism , Verapamil/pharmacology , Acute Disease , Animals , Calcium Channel Blockers/therapeutic use , Calcium Radioisotopes , Cytosol/metabolism , Disease Models, Animal , Drug Evaluation, Preclinical , Endoplasmic Reticulum/metabolism , Male , Mitochondria/metabolism , Myocardial Ischemia/drug therapy , Rats , Verapamil/therapeutic useABSTRACT
The simulation of the hypo- and hyperactivity of the hypophysis-adrenocortical system induced considerable changes in the reactivity of alpha 2-adrenoceptors, as well as in the resistance of the organism to stressful influences. The findings support the assumption that the blockade of alpha 2-adrenoceptors is one of the key features in the adaptive mechanism of the glycocorticoid hormones action.
Subject(s)
Adrenergic alpha-Antagonists/pharmacology , Pituitary-Adrenal System/physiology , Receptors, Adrenergic, alpha/physiology , Stress, Psychological/physiopathology , Acute Disease , Adrenalectomy , Adrenergic alpha-Agonists/pharmacology , Animals , Decerebrate State/physiopathology , Hemorrhage/physiopathology , Hypophysectomy , Hypoxia/physiopathology , Ischemic Attack, Transient/physiopathology , Pituitary-Adrenal System/drug effects , Rats , Receptors, Adrenergic, alpha/drug effects , Restraint, Physical , Sympathectomy, ChemicalABSTRACT
Experiments were conducted on pithed rats with acute pancreatitis and on falsely operated on animals (ether-laparotomy stress) to study the reactivity of vascular alpha 1- and alpha 2-adrenoreceptors and its role in changes in arterial pressure. Selective change in the reactivity of alpha 2-adrenoceptors alone was revealed in both groups. Stable reduction of vascular alpha 2-adrenergic reactivity (by 57-58%) and arterial pressure was recorded in animals with acute pancreatitis. In falsely operated on animals, in contrast, the values of these indices exceeded the control level. In animals with a functioning central nervous system inhibition of alpha 2-adrenergic reactivity correlated with change in arterial pressure only in the initial (3-4 hours) hemorrhagic phase of acute pancreatitis.
Subject(s)
Blood Pressure/physiology , Pancreatitis/physiopathology , Receptors, Adrenergic, alpha/physiology , Acute Disease , Adrenergic alpha-Agonists/pharmacology , Animals , Azepines/pharmacology , Blood Pressure/drug effects , Clonidine/pharmacology , Decerebrate State/physiopathology , Laparotomy , Male , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/physiopathology , Phenylephrine/pharmacology , Rats , Receptors, Adrenergic, alpha/drug effectsSubject(s)
Glycyrrhiza , Hydroxy Acids/isolation & purification , Oleic Acids/isolation & purification , Plants, Medicinal , Stearic Acids/isolation & purification , Stress, Physiological/drug therapy , Adrenalectomy , Animals , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Gas Chromatography-Mass Spectrometry , Hydroxy Acids/analysis , Hydroxy Acids/therapeutic use , Mice , Oleic Acids/analysis , Oleic Acids/therapeutic use , Rats , Stearic Acids/analysis , Stearic Acids/therapeutic useSubject(s)
Adrenal Cortex/physiology , Motor Activity/physiology , Pituitary-Adrenal System/physiology , Posture , Sympathetic Nervous System/physiology , Adrenalectomy , Animals , Hydroxydopamines , Hypophysectomy , Hypothermia, Induced , Male , Oxidopamine , Rats , Restraint, Physical , Sympathectomy, ChemicalABSTRACT
Content of adrenaline, noradrenaline, dopamine and normetanephrine was estimated by means of trihydroxyindole method in samples of brain and its hypothalamic part from intact, adrenal- and sympathectomized rats within 15 min, 24 and 72 hrs after hemorrhagic stress (3% blood of body weight within 20 min). Stable increase in dopamine content was observed in brain at all the periods studied. Alterations in the noradrenaline turnover in central nervous system were related to the state of peripheral sympathoadrenal system at early posthemorrhagic steps; the phenomenon was not found at the later periods after stress.
Subject(s)
Adrenal Glands/physiology , Catecholamines/metabolism , Central Nervous System/metabolism , Hemorrhage/metabolism , Stress, Physiological/metabolism , Sympathetic Nervous System/drug effects , Adrenalectomy , Animals , Dopamine/metabolism , Epinephrine/metabolism , Male , Norepinephrine/metabolism , Normetanephrine/metabolism , Rats , Time FactorsABSTRACT
A new method of compelling rats and mice to perform uninterrupted dynamic work has been devised. The animal, fixed from its tail and situated in vertical position in respect to the surface of the water with which it comes in contact only with its muzzle and forepaws, is compelled to execute uninterrupted muscular work. Total exhaustion is determined by the cessation of muscular activity, as a result of which the animal, choked by water, perishes. The method is suitable for carrying out the screening of pompounds having adaptogenic properties, for studying the mechanism of raising the endurance; it also allows registration of physiological parameters in the course of the experiment.
Subject(s)
Physical Exertion , Adaptation, Physiological , Animals , Fatigue/prevention & control , Mice , Models, Biological , Physical Exertion/drug effects , RatsABSTRACT
Content of adrenaline, noradrenaline, dopamine, DOPA and normethanephrine was estimated by means of the hydroxyindole method in brain tissue and hypothalamic region of rats subjected to hemorrhagic shock (loss of 3% of blood during 20 min) within 15 min, 2, 24 and 72 hrs. At the first day after the hemorrhage an increase in content of adrenaline and a distinct decrease in content of noradrenaline were observed in hypothalamic region, although the biosynthesis the neurotransmitters was not inhibited. Then, the noradrenaline concentration was normalized but the content of its precursors was decreased. In brain a constant posthemorrhagic increase in content of dopamine and the phase alterations in patterns of the catecholamine metabolism were observed: an initial decrease in synthesis and turnover of noradrenaline followed by its increased metabolism.