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Biomedical subjects

A L Markel'

Publications and source records attributed to A L Markel'.

At least 73 records · Page 4Linked to original sources

[Expression of the pro-opiomelanocortin gene in rats with inherited arterial hypertension].

Expression of pro-opiomelanocortin (POMC) gene in pituitary of rats from newly developed hypertensive strain (ISIAH strain) was studied by dot hybridization. The pUC8 plasmid containing 900 base pair (bp) segment or the human POMC gene corresponding to the major portion of the 3'-nontranslated mRNA region and 60 bp coding for the signal peptide, was used as a probe for hybridization. It was found that the expression of the POMC in pituitary of the hypertensive JSJAH rats was more than 3-fold gene lower as compared to normotensive Wistar strain. The latter is the original strain from which the ISIAH rats were bred. The mechanism of this phenomenon and its possible relation to the arterial hypertension are discussed.

Animals↗

[Brain adrenoreceptors in rats with inherited arterial hypertension due to emotional stress].

For the study of genetic and physiological mechanisms of inherited stress-sensitive arterial hypertension, specific binding of ligands of alpha 1-, alpha 2- and beta-adrenoceptors was measured in 2 strains of rats: Wistar normotensive and ISSAH rats (rats with inherited stress-sensitive arterial hypertension). The maximal binding sites (Bmax) and apparent dissociation constants (Kd) were studied with the alpha 1-adrenergic antagonist 3H-prazosin, alpha 2-adrenergic agonist 3H-clonidine and 3H-dihydroalprenolol, a beta 1-receptor antagonist. Four brain regions were investigated: frontal cortex, hypothalamus, pons and medulla oblongata. In comparison with normotensive controls, hypertensive rats had significantly greater density of the alpha 1-adrenoceptors in the medulla oblongata. However, the number of hypothalamic alpha 1-adrenoceptors was significantly reduced in these animals. The same significantly lower alpha 2-adrenoreceptor density was found in the hypothalamus and the pons, and lower, beta-adrenoceptors density in the medulla oblongata. It was concluded that brain adrenoceptors are involved in the mechanisms of development of inherited stress-sensitive hypertensive syndrome.

Animals↗

The biochemical characteristics of stress-sensitive hypertensive rats.

The biological characteristics of a line of stress-sensitive hypertensive (SSH) rats genetically selected from Wistar rats are described, in particular the dynamics of arterial blood pressure and the biochemical properties of the Na(+)-K+ ATPase present in the outer renal medulla. Changes in the specific activity of this enzyme are discussed in terms of the lipid composition of the membrane bilayer and the amount of endogenous ouabain-like compounds present in the blood of the animals under study. Rats of both strains, Wistar and SSH, were studied under conditions of rest and stress (8 day regime of daily 30 min immobilization). The production in vivo of adrenal mineralocorticoids and glucocorticoids is estimated and several biochemical features of the pathogenesis of essential hypertension are discussed.

Adrenal Cortex Hormones↗

[Endocrine-metabolic relations in rats with genetic arterial hypertension].

Levels of triiodothyronine, thyroxine, insulin, glucose and free fatty acids in the blood; contents of adrenaline, noradrenaline in adrenals and glycogen in the liver; activity of phenylethanolamine-N-methyltransferase in adrenals, hexokinase and glucose-6-phosphatase in the liver were studied in male Wistar rats and rats with inherited stress-induced arterial hypertension /ISIAH/. It was found that genetically caused rise of hypophyseal-thyroid systems activity in ISIAH-rats leads to a decrease of insulin blood level, activation of lipolysis and breach of glucose tolerance.

Adrenal Glands↗

[Differences in serotonin receptor types I and II binding in the brain regions of rats with 2 types of hereditary arterial hypertension].

Serotonin C1- and C2-receptor binding was studied in various segments of the brain in two strains of rats with hereditary arterial hypertension--spontaneously hypertensive (SHR) and hereditary stress-induced hypertensive rats (HSIHR). In the hypothalamus, there was a higher C1-receptor binding in HSIHR than in Wistar rats. SHR showed a higher C2-receptor binding in the cortex and C1-receptor one in the pons than did HSIHR. The changes found are suggestive of both similarities and differences in the serotonin receptor system in the two strains of rats with hereditary arterial hypertension.

Animals↗

[Endocrine and lymphoid interrelations in rats with hereditary arterial hypertension].

Functional state of the adrenals and structural organization of the thymus and lymph nodes in the rats with hereditary stress-induced arterial hypertension (HSIAH) have been investigated in the control and against the background of a prolonged staying under conditions of a moderate cold. In comparison with the initial population of Wistar rats, the test animals demonstrate an elevated level of corticosterone, decreased mass and size of the thymus, the size of the popliteal lymph nodes is increased at the expense of the structural components of the medulla. In 7 weeks of living in cold secretion of adrenal steroids in Wistar rats increases greatly and it is noticeably less in the HSIAH rats. Structural changes in the thymus are also insignificant, but reaction of the lymph nodes is important. Their size sharply diminishes at the expense of certain structural components of the medulla. A shift towards mature forms of the plasmocytic line cells takes place.

Adrenal Glands↗

[The hypothalamo-hypophyseal neurosecretory system in rats with hereditary arterial hypertension].

Histochemical and cytometrical analysis of the peptidergic Gomori-positive or hypothalamo-hypophyseal neurosecretory system (HHNS) was made in the 3 strains of rats: spontaneously hypertensive rats (SHR), rats with inherited stress-induced arterial hypertension (ISIAH), and normotensive Wistar rats. A significant increase in the production of the peptide neurohormones by the supraoptic nuclei was found in two hypertensive strains (SHR and ISIAH) compared to the normotensive Wistar rats. For ISIAH-rats, the excretion of neurohormones was more pronounced in the region of median eminence, and for SHR--in the posterior hypophyseal lobe. It was concluded that hyperfunction of HHNS can play an important role in the hypertension development in two strains or rats studied.

Animals↗

[Effect of color mutation on the function of the adrenal cortex in chronic feed stress in American mink].

Effect of color mutations, headlund and aleutian, on the adrenocortical function was studied in American mink under stress conditions. The adrenocortical function was analysed in the course of gland's incubation in vitro. Natural environmental factors (sharp fall of temperature) and artificially limited feed served as stress factors. It was shown that minks heterozygous for color mutant alleles studied were more resistant to the stressors. This is associated with genetically mediated peculiarities of the action of hypophysial adrenocortical system which is characterized by more adequate reactivity towards stimuli acting. Thus, the effect of heterosis in minks heterozygous for color alleles may well be caused by their increased resistance to stress.

Adrenal Cortex↗

[Correction of arterial pressure in rats with hereditary hypertension by altering catecholamine metabolism in early ontogeny].

In a newly developed rat strain with inherited stress-sensitive arterial hypertension (ISSAH) an attempt was made to reduce arterial blood pressure by L-DOPA injections during a short time period of the early ontogenesis. It was shown that L-DOPA injections to rats on days 7-9 or 14-16 of life had no effect. The same procedure performed on 21-23 or 21-25-day-old rats was followed by a decrease in the basal and stress-induced arterial blood pressure levels, measured in adulthood. Injections of dopamine-beta-hydroxylase inhibitor (FLA-59) with parallel L-DOPA administration completely blocked the blood pressure decreasing effect. It can be suggested that injections of L-DOPA in the 4th week of post-natal life reduce the blood pressure level in ISSAH rats by enhancing the rate of brain noradrenaline biosynthesis.

Aging↗

[Prenatal hydrocortisone modification of the adrenocortical function of adult rats with hereditary arterial hypertension].

The adrenocortical function of adult normotensive (Wistar) and hypertensive rats with hereditary stress-induced arterial hypertension was studied after the injection of hydrocortisone to their mothers on the 16th and 18th days of gestation. Prenatal hydrocortisone treatment decreased adrenocortical reactivity to emotional stress or to intracerebroventricular injection of norepinephrine in adult Wistar rats, but did not modify the reaction to stress induced by bleeding, ether anesthesia or central stimulation with carbocholine. Hormonal treatment did not change the reactivity of rats with hereditary stress-induced arterial hypertension to both stress factors employed, enhanced it by intracerebral norepinephrine injection but decreased it by carbocholine intracerebroventricular injection. Thus, the interstrain differences in the modification action of the hormones were observed. These differences may be caused by peculiar brain organization of hypertensive rats, namely their decreased reactivity to norepinephrine.

11-Hydroxycorticosteroids↗

[Reactivity of the hypothalamo-pituitary-adrenocortical system in rats with hereditary arterial hypertension].

The function of hypothalamo-hypophyseal-adrenocortical system was studied in rats with inherited stress-sensitive arterial hypertension (ISSAH). The rats have been bred from the outbred Wistar strain. It was found that plasma corticosteroid level in ISSAH rats was lower after immobilization stress and higher after stress induced by a combination of stress-factors (ether, 0.7 ml blood loss, novel situation), as compared to Wistar rats. ISSAH rats also showed a reduced reaction to intracerebroventricular noradrenaline (10 micrograms) injection. It was concluded that the changes of noradrenergig brain mechanisms can be responsible for the alterations in the central regulation of blood pressure and adrenocortical function in ISSAH rats.

11-Hydroxycorticosteroids↗

[Characteristics of the central adrenergic mechanisms regulating arterial pressure in rats with hereditary arterial hypertension].

Adrenergic mechanisms of blood pressure regulation were studied in a newly developed strain of rats with inherited stress-provoked arterial hypertension, spontaneously hypertensive rats (SHR) and normotensive Wistar rats. A number of adrenergic agonists (noradrenaline, adrenaline, phenylephrine, clonidine, naphazoline, isoproterenol, dobutamine, Alupent) were infused into the lateral brain ventricle under nembutal anesthesia and the reaction of the peripheral blood pressure was measured. It was shown that blood pressure reactions were similar in rats with inherited stress-provoked arterial hypertension and in SHR but significantly differed from those of normotensive Wistar rats. The data obtained suggest that the development of inherited hypertension was accompanied by changes in alpha 1 to alpha 2 adrenoreceptor ratio in pressor and depressor brain regions. A decrease in the depressor effect after stimulation of beta 1 and beta 2 receptors has been also observed.

Animals↗

[Adrenaline-induced damage to the myocardium in rats with genetically determined arterial hypertension].

Genetically hypertensive and normotensive rats were subjected to acute myocardial injury by a single subcutaneous injection of adrenaline (0.5 mg/100 g bw). The animals were sacrificed one day later. The lesions showed the signs of focal coagulative necrosis and intracellular myocytolysis. The damaged cardiomyocytes with high sarcolemmal permeability for blood plasma proteins were more widespread in the hypertensive versus normotensive rats. Intracellular myocytolysis, which is not associated with alterations in the cell membrane, was found in both experimental groups at an equal rate. The data agree with the concepts of alterations in biological membranes in genetically determined arterial hypertension.

Animals↗

[Hybrid analysis of adrenocortical function in laboratory rats].

The adrenocortical function in two inbred strains of rats, Wistar (WAG) and August (AUG), and their F1, F2 and backcross hybrids was studied. The parental strains differed by the adrenal weight, plasma corticosterone level and in vitro adrenal secretion rate. Additive-dominant model of Mather and Jinks for the data analysis was applied. It was shown that genetic determination of the adrenocortical function was characterized by both intra- and inter-loci nonadditive and partly additive interactions. A genotype-environment interaction and a high environmental variance for some traits have been found. Under a stressful stimulation, the most significant additive genetic variance for plasma corticosterone level was revealed. This result completely coincides with our early conclusion about the role of the stress in manifestation of genetic variability. It may be concluded that the genotype integrity is a very important factor in determining the adrenocortical function of laboratory rats.

11-Hydroxycorticosteroids↗

[Genetic problems of stress. V. The genetics of adrenal cortical reactivity in emotional stress in rats].

Genetic analysis of adrenocortical reactivity (the level of plasma corticosterone and secretion of the adrenal gland in vitro) was carried out under conditions of emotional stress in three inbred strains of rats (Wistar, August, Sprague-Dawley) and in their F1 reciprocal hybrids. The basal adrenocortical function was similar in genotypes studied. However, significant genotype-dependent variability was demonstrated under conditions of stress stimulation. The variability of adrenal secretion in vitro was mediated by genes displaying an additive action, while variability in the level of plasma corticosterone included components both of general combining ability and of specific combining ability. Also, the role of a reciprocal effect was noted. The peculiarities of genetic determination of adrenocortical reactivity to emotional stress are discussed.

11-Hydroxycorticosteroids↗

[Effect of stress in early ontogeny on the circadian rhythm of rat corticosteroid function].

The effect of short-term stress (cooling) during different periods of early ontogenesis on the characteristics of circadian rhythm of the corticosteroid function in adult animals were studied in the experiments with rats. The stressing of 2--4 and 17--19 days old rats was shown to modify the phase characteristics of circadian rhythm of the basal function of suprarenals in the adults. The circadian characteristics of reaction of the adults to stress suffered respective changes. The stimulation in the early ontogenesis did not affect the function of isolated suprarenals, thus suggesting that the changes in phase characteristics of circadian periodicity of the corticosteroid function are based on the influence of early stress effects on the regulatory system of this function. The pattern of early stress effects modifying the rhythm depends on the age of animals under stress.

11-Hydroxycorticosteroids↗

[Evaluation of the basic characteristics of rat behavior in the "open field" test].

Heart rate, motor activity and defecation were studied in rats of the Wistar strain in 10 successive one-hour "open field" tests. Defecation and heart rate parameters decreased monotonously both from test to test and throughout one session. In motor activity a second rise was recorded at 6--12th minutes against the background of a gradual decline. A positive correlation between the total value of defecation and the heart rate in 2nd-3rd minutes of the first test was observed. At the 13th minute the motor activity positively correlated with the heart rate. Significant negative correlation between motor activity and total value of defecation appeared only at 10--11th minutes of the first test. A conclusion is drawn on twofactorial motivational basis of rats' behaviour in the "open field" test.

Animals↗