Aldehydes and disturbance of carbohydrate metabolism: some consequences and possible approaches to its normalization.

There are many well-documented errors of metabolism involving genetic defects that affect carbohydrate utilization. The array of disorders includes the defective utilization of glucose, as well as enzymatic deficiencies in glycolysis and gluconeogenesis, and the pentose phosphate pathway. Besides, there is considerable literature about metabolic syndrome and diabetes. However, the main problem of their origin remains obscure. Also, it is presently beyond doubt that there are various causes of insulin resistance. The development of insulin resistance may be associated not only with insulin production disorders or presence of insulin antagonists but also with modification of the number of receptors and sensitivity of peripheral tissues. The insulin resistance originates from insulin signal transmission defects at its initial stages. It is presently uncertain which mechanisms of adaptation regulation are activated or should be activated under hyperglycemia conditions. This is the main problem of the selection of strategy of hyperglycemia treatment but it is important that aldehydes - the secondary products of lipid peroxidation and protein glycation (malondialdehyde and methylglyoxal) - make a contribution to abnormal metabolism. As far as the role of methylglyoxal in inhibition of antioxidant enzymes is concerned, the involvement of the ketoaldehyde in such processes as oxidative stress, cell proliferation control, and carbohydrate metabolism disorders does not cast any doubt.

Effects of chronic neuroticization on the monoaminergic systems of different structures in the brains of rats with different typological characteristics.

The levels of monoamines and their metabolites were studied by HPLC with electrochemical detection in homogenates of hypothalamus, hippocampus, prefrontal cortex, and amygdala in intact and neuroticized Wistar rats with different types of behavior in the open field and forced swimming tests. Intact rats with intermediate levels of activity and depressivity had higher serotonin concentrations in the hypothalamus and lower noradrenaline and hydroxyindoleacetic acid levels in the hippocampus than rats characterized by low activity and high depressivity. In neuroticization, the levels of study monoamines and their metabolites decreased in all the brain structures investigated with the exceptions of an increase in the dopamine concentration in the hippocampus and the dihydroxyphenylacetic acid concentration in the prefrontal cortex. The effect of neuroticization on the neurotransmitter systems in all study structures except the hypothalamus depended on the typological characteristics of the rats. This was most marked in rats with the extreme types of behavior--active and passive--in which changes in monoamine and metabolite contents were seen in all brain structures studied. Rats of the intermediate type showed no changes in any of the substances studied in the hippocampus.

[The influence of chronic neurotization on the monoaminergic systems of various brain structures in rats with various typological characteristics].

Typological behavioral features of Wistar rats were tested in the open field and in Porsolt test. Rats were assigned to groups with high (HAct), medium (MAct), and low (LAct) behavioral activities. The same rats were assigned to high (HDep), medium (MDep) and low depressive (LDep) groups. The release of norepinephrine, dopamine, serotonin and their metabolites in homogenates obtained from the hypothalamus, hippocampus, frontal cortex and amygdala was assessed by microdialysis and HPLC. In these groups, the monoamine concentrations were different: the level of serotonin was higher in the hypothalamus and norepinephrine and 5-HIAA levels were lower in the hippocampus of MAct - MDep rats as compared to LAct - HDep. Chronic neurotization caused changes in monoamine concentrations in the hypothalamus and amygdala in rats of all groups, whereas in the hippocampus and frontal cortex monoamine changes were observed in HAct - LDep and LAct -HDep rats. The most prominent changes in monoamines levels in neurotized rats with different types of behavior were found in the frontal cortex, amygdala and hippocampus. The results show a correlation between the typological of behavioral characteristics and the reaction to stress of monoaminergic systems of the hypothalamus, hippocampus, frontal cortex and amygdala.

Effects of electrical stimulation of vagal nuclei in anesthetized and unanesthetized cats.

Changes in the heart rate were studied during stimulation of the effector nuclei of the vagus nerves--the dorsal vagal nucleus and the nucleus ambiguus--in anesthetized and unanesthetized cats. If groups of neurons, stimulation of which in anesthetized cats causes slowing of the heart, were stimulated in unanesthetized cats under conditions of free behavior, the heart rate was increased. Pharmacological beta-adrenergic receptor blockade by injection of Obsidan or Inderal (propranolol) demonstrated the parasympathetic nature of these effects. The fact that they are parasympathetic in nature was also confirmed by the character of the response: its short latent period and rapid disappearance of the effect after removal of the stimulation.

[Hemodynamic mechanisms of the hypotensive effect of cobalt in anesthetized rats]. / Gemodinamicheskie mekhanizmy gipotenzivnogo deistviia kobal'ta u narkotizirovannykh krys.

Hemodynamic mechanisms of Co(2+)-evoked hypotension were studied in pentobarbital--anesthetised male Wistar rats. Bolus i.v. administration of cobalt sulphate (30, 90 and 270 mg/kg of Co) evoked dose-dependent hypotension followed by tachycardia and increase in left ventricular contractility index (dP/dt/P). Administration of beta-adrenoblocker propranolol (2 mg/kg) attenuated Co evoked (270 ug/kg) tachycardia and unmasked its cardiodepressive effects (dP/dt/P decreased by 11% and end-diastolic pressure increased by 55%). Cardiodepressive Co2+ effects were prevented by administration of verapamil (0.4 mg/kg). In the second group hemodynamic mechanisms of Co-evoked hypotension were studied with radioactive microspheres. Co2+ infusion (55 mg/kg) lowered blood pressure (in average by -11%) by decreasing total peripheral resistance (-25%). Cardiotoxic effects were obtained with a ++larger dose 80 mg/kg/min. It is concluded that Co decreased blood pressure by vasodilatator action and its cardiotoxic effects attenuated by sympathetic counterregulation and may be prevented by verapamil.

[Various hemodynamic mechanisms of the hypertensive reaction in immobilization-induced stress in rabbits and rats]. / Razlichnye gemodinamicheskie mekhanizmy gipertenzivnoi reaktsii pri immobilizatsionnom stresse u krolikov i krys.

The radioactive microsphere technique was used to measure the cardiac output, regional blood flows and resistances in conscious rabbits and rats before and after 30-minute immobilization. Immobilization evoked blood pressure rise in both species. Cardiac output was reduced and total peripheral resistance increased in rabbits. Reverse changes of these parameters were observed in rats. Blood flow was reduced in the liver and the right ventricle in rabbits, and in the testes in rats. In immobilized rats, regional blood flow increased in skeletal muscles, the heart, the adrenals and the liver. These experiments demonstrate different hemodynamic mechanisms of immobilization-induced hypertension in rabbits and rats.

[Changes in systemic and regional hemodynamics in the acute period of myocardial infarction in conscious rabbits]. / Izmeneniia sistemnoi i regionarnoi gemodynamiki v ostrom periode infarkta miokarda u bodrstvuiushchikh krolikov.

Systemic and regional hemodynamics (radioactive microspheres of 15 mcm) were studied in 7 conscious immobilized rabbits 30 min, 24 and 72 hours after left coronary artery occlusion (group 1) and 30 min and 24 hours after the occlusion in 5 rabbits who died the next day (group 2). Significant changes in myocardial blood flow, white cerebral matter and kidneys were only observed 24 h after coronary artery occlusion in group 2, simultaneously with a significant (29%) decrease in cardiac output. It is suggested that significant regional blood flow changes associated with acute experimental myocardial infarction only occurred in the presence of heart failure in rabbits.

[Comparative study of hemodynamic effects of antidepressants (tetrindole and desipramine) during immobilization stress in hypertensive rats]. / Sravnitel'noe izuchenie gemodinamicheskikh éffektov antidepressantov (tetrindola i dezipramina) pri immobilizatsionnom stresse u gipertenzivnykh krys.

Tetrindole (a tetracyclic antidepressant, reversible MAO inhibitor of the A type) and desipramine (a tricyclic antidepressant, nonselective inhibitor of the reverse catecholamine trapping) produce opposite hemodynamic effects in stroke-prone hypertensive rats (SHR-SP): tetrindole reduced, whereas desipramine increased, the heart rate and arterial pressure. Under the acute immobilization stress conditions in SHR-SP, tetrindole inhibited development of the post-stressor tachycardia, while desipramine did not change the heart rate and increased the arterial pressure.

[Differences in the redistribution of cardiac output during hyperthermia in waking rats and guinea pigs]. / Razlichiia v pereraspredelenii serdechnogo vybrosa pri gipertermii u bodrstvuiushchikh krys i morskikh svinok.

The heat stress induced common responses in rats and guinea pigs: an increase in the blood flow at the sites of heat radiation and in the diaphragm, and its decrease in splanchnic area's organs and in kidneys while cardiac output remained constant. The species differences occurred in the responses of intestine and skeletal muscles' vessels. The differences seem to be due mainly to the differences in behavioral responses to the heat stress in these animals.

[Changes in the systemic and regional hemodynamics, hydration and engorgement of the lungs during occlusion of the thoracic aorta]. / Izmeneniia sistemnoi i regionarnoi gemodinamiki, ovodneniia i krovenapolneniia legkikh pri okkliuzii aorty v grudnom otdele.

The occlusion of the rat aorta's thoracic portion induces within 30 min hemodynamic shifts in major and minor circulation typical for a hypertensive incident. The occurring 4-5-fold increase of the lung venous pressure leads to no regular lung oedema and is of no major importance for its pathogenesis.

[Antifibrillatory effect of the calcium antagonist foridon in acute myocardial ischemia in conscious rabbits]. / Antifibrilliatornoe deistvie antagonista kal'tsiia foridona pri ostroi ishemii miokarda u bodrstvuiushchikh krolikov.

The effect of ryodipine on disorders of rhythm induced by occlusion of the left descending coronary artery was studied in experiments on 40 conscious immobilized rabbits. Ryodipine was injected intravenously (50 mcg/kg 5 minutes prior to and 25 mcg/kg after occlusion). Ventricular fibrillation developed in 19 (66%) rabbits of the control group and in 3 (27%) animals in the experimental group (p less than 0.03). The parameters of systemic and regional hemodynamics were studied in 7 rabbits of the control group and in 5 animals of the experimental group before and 30 minutes after occlusion; microspheres (15 mcm) labelled with various radioactive isotopes were used in the study. The blood flow in the intact myocardium of rabbits given ryodipine was higher than the initial level by 14% (p less than 0.05). The coronary fraction of the cardiac output increased by 21%. It is concluded that the antifibrillation effect of ryodipine is due to its favourable action on the myocardial blood flow.

[The regulation of systemic and regional hemodynamics in waking rats with a chronic adriamycin-induced myocardial lesion]. / Reguliatsiia sistemnoi i regionarnoi gemodinamiki u bodrstvuiushchikh krys s khronicheskim adriamitsinovym porazheniem miokarda.

Rats were given intraperitoneal injections of adriamycin (cumulative dose 20 mg/kg). Two weeks after the last injection left-ventricular function and systemic and regional hemodynamics were studied before and during isoprenaline infusion (0.64 mcg/kg/min) in conscious rats with no signs of cardiac insufficiency. In the controls isoprenaline increased the left-ventricular contractility index by 45% and the heart rate by 30%. The contractility index in rats given adriamycin did not change, the heart rate increased only by 14%, but in contrast to the controls, a significant increase of the cardiac index by 36% and diminution of total peripheral resistance by 36% were revealed. The sensitivity of the baroreflex chronotropic component in the control animals was twice that in the experimental rats. It is concluded that adriamycin cardiomyopathy in rats is attended by reduced sensitivity of the baroreflex mechanisms and diminished myocardial adrenergic reactivity.

[Systemic and regional hemodynamics in alert rats with increasing hyperthermia]. / Sistemnaia i regionarnaia gemodinamika u bodrstvuiushchikh krys v usloviiakh narastaiushchei gipertermii.

The changes in the parameters of systemic and regional hemodynamics during thermal stress were followed up in awake male Wistar rats. The cardiac output (CO) and blood flow in 16 zones of the body were measured by means of 15 microns microspheres labeled by 4 different isotopes. The blood flow increased in the skin of the tail, the liver, heart, adrenals, and skeletal muscles and reduced in the organs of the splanchnic region and kidneys. When body temperature reached 42 degrees C the CO decreased. The shifts in the regional blood flow maintained their direction, with the exception of a sharp increase of blood flow in the small intestine which preceded or coincided with the beginning of a fall in arterial pressure. The rate of increase of left ventricular pressure remained at a high level. It is assumed that the disruption of celiac vasoconstriction is among the earlier developing links of hemodynamic disorders in thermal affections and is caused by the vasodilative effect of the factors of local control of the vascular functions.