Hereditary Stress-induced Arterial Hypertension Research Articles

Urine metabolic profile in rats with arterial hypertension of different genesis.

The diversity of pathogenetic mechanisms underlying arterial hypertension leads to the necessity to devise a personalized approach to the diagnosis and treatment of the disease. Metabolomics is one of the promising methods for personalized medicine, as it provides a comprehensive understanding of the physiological processes occurring in the body. The metabolome is a set of low-molecular substances available for detection in a sample and representing intermediate and final products of cell metabolism. Changes in the content and ratio of metabolites in the sample mark the corresponding pathogenetic mechanisms by highlighting them, which is especially important for such a multifactorial disease as arterial hypertension. To identify metabolomic markers for hypertensive conditions of different origins, three forms of arterial hypertension (AH) were studied: rats with hereditary AH (ISIAH rat strain); rats with AH induced by L-NAME administration (a model of endothelial dysfunction with impaired NO production); rats with AH caused by the administration of deoxycorticosterone in combination with salt loading (hormone-dependent form - DOCA-salt AH). WAG rats were used as normotensive controls. 24-hour urine samples were collected from all animals and analyzed by quantitative NMR spectroscopy for metabolic profiling. Then, potential metabolomic markers for the studied forms of hypertensive conditions were identified using multivariate statistics. Analysis of the data obtained showed that hereditary stress-induced arterial hypertension in ISIAH rats was characterized by a decrease in the following urine metabolites: nicotinamide and 1-methylnicotinamide (markers of inflammatory processes), N- acetylglutamate (nitric oxide cycle), isobutyrate and methyl acetoacetate (gut microbiota). Pharmacologically induced forms of hypertension (the L-NAME and DOCA+NaCl groups) do not share metabolomic markers with hereditary AH. They are differentiated by N,N-dimethylglycine (both groups), choline (the L-NAME group) and 1-methylnicotinamide (the group of rats with DOCA-salt hypertension).

The condition of the intracellular metabolism of peripheral blood leukocytes in arterial hypertension (experimental study)

Objective: the comparative analysis of the features of intracellular metabolism of polymorphonuclear leukocytes (PNL) in the peripheral blood of rats with the normal blood pressure and hereditary stress-induced arterial hypertension (ISIAH). Material and methods. Indicators of carbohydrate and lipid metabolism, activity of some key redox enzymes in leukocytes of rats as well as a level of PNL functional activity were examined by histochemical methods. Results. The study determined that the stable increased blood pressure is accompanied by hypertrophy of the left ventricle of the heart, degenerative changes in cardiomyocytes and the decreased microcirculatory bed density. In this case amount of intracellular glycogen in leukocytes was decreased in 23% at unchanged amount of intracellular lipids. Activities of intracellular ATP-ase and myeloperoxidase were reduced in 22% with non-significant increasing of succinate dehydrogenase activity (in 13%). Amount of PNL with positive NBT-test was increased in 35% in the rats of ISIAH. Conclusions. Analysis of the studied metabolic indicators of PNL shows disturbance of the energy-supplying and enzymatic processes in the leukocytes on the background of arterial hypertension.

Comparison of Reactivity of the Lipid Peroxidation-Antioxidant Defense System in Normal and Hypertensive Rats at Different Stages of Stress-Reaction.

We compared changes in the parameters of LPO-antioxidant defense system at various stages of the stress response in mature male ISIAH rats (hereditary stress-induced arterial hypertension) and WAG rats in 3 h (stage of anxiety) and 7 days (resistance stage) after a 3-h single immobilization in the supine position. It was found that post-stress reactivity of the nonspecific stress-limiting LPO system is different in normotensive and hypertensive rats. ISIAH rats, irrespective of the stage of the stress-reaction, demonstrated more intense LPO reactions (accumulation of TBA-reactive products) and reduced antioxidant defense parameters (low content of lipid-soluble vitamins, increased oxidized glutathione content) in comparison with the corresponding parameters in WAG rats.

Age-related structural characteristics of the adrenal medulla in hypertensive NISAG rats

Structural characteristics of the adrenal medulla in hypertensive NISAG rats (hereditary stress-induced arterial hypertension) were studied during various periods of postnatal ontogeny. Signs of hyperplasia of the adrenal medulla were most pronounced in adult hypertensive animals with persistent arterial hypertension, as well as during the period of late ontogeny.

Peculiarities of active avoidance conditioning in rats with various forms of inherited arterial hypertension

Peculiarities of active avoidance conditioning were studied in NISAG rats (hereditary stress-induced arterial hypertension) and spontaneously hypertensive SHR rats. Conditioning was successful in 90% normotensive Wistar rats and in only 9.1% NISAG rats. Hypertensive SHR rats were intermediate between Wistar and NISAG rats by their learning capacity (66.7%). Our results suggest that differences in learning capacity of hypertensive rats are determined by genetic characteristics of animal behavior and emotional state, rather than blood pressure elevation.

Activity of 11β-hydroxysteroid dehydrogenase in tissues of hypertensive NISAG rats

11beta-Hydroxysteroid dehydrogenase activity in the kidneys of NISAG rats (rat strain with hereditary stress-induced arterial hypertension) was 1.5-fold higher than in WAG rats. An inverse relationship was observed in the liver of these animals. After stress exposure 11beta-hydroxysteroid dehydrogenase activity remained unchanged in the kidneys of NISAG and WAG rats, but significantly increased in the liver of NISAG rats. Functional activity of 11beta-hydroxysteroid dehydrogenase probably reflects the hypertensive state of NISAG rats.

Activity of Angiotensin-Converting Enzyme in Hereditary Stress-Induced Arterial Hypertension

We measured activity of angiotensin-converting enzyme in plasma and tissue of NISAG and normotensive WAG rats. In different organs of NISAG rats, activity of this enzyme did not differ from the corresponding values of WAG rats, although enzyme activity in the plasma of NISAG rats was significantly lower than that of WAG rats. Since NISAG rats are characterized by low activity of renin in the renal cortex, it is hypothesized that NISAG rats simulate the low-renin hypertension, in which inhibition of activity of the angiotensin-production system results from elevation of arterial pressure of central origin.

Effect of neonatal handling in rats with hereditary stress-induced arterial hypertension (NISAG rats).

NISAG rats were subjected to handling on days 1-21 after birth. Blood pressure and plasma corticosterone concentration were measured in 6-month-old handled and control NISAG rats at rest and under stress conditions. Animal behavior was studied in the open-field test. Handling had no effect on body weight and relative weights of the heart and adrenal glands. In rats subjected to handling, changes in blood pressure and adrenal cortex produced by acute emotional stress (30-min restriction) were less pronounced than in control animals. Handled rats demonstrated less fear in a new environment and exhibited high exploratory activity in the open-field test. Our findings suggest that neonatal handling reduces stress reactivity and decreases the severity of hypertension in adult NISAG rats.

Hypotensive effect of potentiated antibodies to angiotensin II and AT1 receptors.

Hypotensive activity of ultralow doses of antibodies to angiotensin II and its receptors was studied on adult NISAG rats with hereditary stress-induced arterial hypertension. Antibodies to C-terminal fragment of angiotensin II receptors produced the most pronounced hypotensive effect, which was reproducible after repeated administration. These antibodies decreased systolic blood pressure by 16.40 +/- 0.62 mm Hg. The most rapid hypotensive effect was produced by affinity purified antibodies to angiotensin II: 2 h after administration of these antibodies systolic blood pressure decreased by 12.80 +/- 5.49 mm Hg. Our results indicate that combination treatment with ultralow doses of antibodies to angiotensin II and its receptors hold much promise for the use in clinical practice.

Hypotensive activity of ultralow doses of antibodies to factors involved in the regulation of vascular tone.

Hypotensive activity of ultralow doses of antibodies to some endogenous substances involved in the regulation of vascular tone was studied on NISAG rats with hereditary stress-induced arterial hypertension. It was found that antibodies to angiotensin II and its receptor in ultralow doses markedly reduced systolic blood pressure, which was reproducible after repeated treatment. The course of peroral treatment with antibodies to endothelin and endothelial NO synthase in ultralow doses did not decrease systolic blood pressure.

Effect of chronic stress during early postnatal ontogeny on structural characteristics of the myocardium and glomerular apparatus of the kidneys in NISAG rats.

We studied structural characteristics of the myocardium and glomerular apparatus of the kidneys in 3-week- and 6-month-old male NISAG rats (hereditary stress-induced arterial hypertension) subjected to handling on days 1-21 of postnatal ontogeny. The animals were daily isolated from mothers for 10 min. Handling did not modulate the development of arterial hypertension and typical morphological signs in the myocardium and kidneys.

Thermoregulatory reactions to cooling in rats with hereditary arterial hypertension.

Experiments on rats with hereditary stress-induced arterial hypertension showed that hypertension shortened the latency and increased the amplitude of constrictive reaction of skin blood vessels to rapid cooling characterized by more rapid and considerable increase in blood norepinephrine content compared to slow cooling. Decreased thermal threshold of metabolic reaction suggests that arterial hypertension is accompanied by changes in both the vascular walls and tissues involved in metabolic reaction to cooling.

Hypothalamo-pituitary-adrenocortical function in the ontogenesis in rats with hereditary stress-induced arterial hypertension

Functional activity of the hypothalamo-pituitary-adrenocortical system (HPAS) was evaluated over time in rats with hereditary stress-induced arterial hypertension (HSIAH) and normotensive Wistar rats. Peripheral blood plasma corticosterone was measured in rats aged 2, 3, 4, 6, 8, 10, 12, and 18 weeks at rest and after 1-h immobilization in perforated cylinders by competitive protein binding. Basal corticosterone level and HPAS reaction to stress were lower in hypertensive rats than in Wistar rats of the same age. The only exclusion was the age of 4 weeks, when hypertension starts to form in HSIAH rats and their HPAS is more sensitive to emotional stress than that of Wistar rate, this sensitivity being associated with increased adrenal reaction to ACTH. Decreased HPAS reaction to emotional stress in adult HSIAH rats was not associated with disorders in adrenal sensitivity to ACTH.

Selenium content and blood antioxidant activity in rats with hereditary arterial hypertension during experimental myocardial infarction.

The dynamics of selenium content in the plasma, lymph, and myocardium and plasma antioxidant activity were studied in male NISAG (hereditary stress-induced arterial hypertension) and Wistar rats with acute myocardial infarction and during recovery. In NISAG rats the decrease in selenium content correlated with the decrease in antioxidant activity. This probably aggravates the symptoms of experimental myocardial infarction in animals with hereditary arterial hypertension.

Structure of renal glomeruli in hypertensive NISAG rats reared by normotensive females.

Morphometry of ultrastructural components of renal glomeruli in 3-week- and 6-month-old rats with hereditary stress-induced arterial hypertension (NISAG rats) reared by normotensive Wistar females showed deceleration of the development of arterial hypertension in NISAG rats and attenuated its negative consequences for kidneys as the target organs.

Morphological peculiarities of juxtaglomerular apparatus of the kidney in rats with hereditary stress-induced arterial hypertension (NISAG rats)

Structure of juxtaglomerular apparatus of the kidney in NISAG rats and morphometric parameters of renin-producing juxtaglomerular, cells of afferent arterioles attest to its activation.

Content of HSP70 in rats with hereditary stress-induced arterial hypertension

Sensitivity of normotensive Wistar rats and NISAG rats (with hereditary arterial hypertension) to heat stress is compared at the organism and cell levels. High temperature sensitivity of NISAG rats correlates with a low content of the main heat shock protein HSP70. This relationship can serve as a biochemical marker of predisposition to arterial hypertension.

Age-related alterations in brain α1-adrenoceptors of hypertensive rats: Their possible role in the development of arterial hypertensionof hypertensive rats: Their possible role in the development of arterial hypertension

The binding of labeled agonist (3H-prazosin) to α1-receptors in the frontal cortex, hypothalamus, and medulla oblongata of hypertensive (NISAG) and normotensive (Wistar) rats of different age is studied to elucidate the role of these receptors in the development of hereditary stress-induced arterial hypertension. It is found that the density of α1-adrenoceptors in the hypothalamus of 30-day-old and adult NISAG rats is decreased, while in the medulla oblongata the number of these receptors, starting from the first week of life, is greater than in Wistar rats of the same age. From a comparison of these findings with the development of hypertension in NISAG rats it is concluded that α1-adrenoceptors of the medulla oblongata are involved in this process.