Spontaneous and orienting-exploratory motor activity in rats with hereditary arterial hypertension

In rats of spontaneously hypertensive line (SHR) in comparison with normotensive animals of WKY line an increased activity was revealed in new surroundings in conditions of open illuminated space, and reduced activity in limited darkened space with weakened extinction of activity. Male SHR rats had a higher daily motor activity and SHR females--a lower level of defecation. The revealed behavioural changes testify to an enhancement of investigatory motivation and weakening of "fear" in SHR rats as well as to increased excitatory and decreased inhibitory processes in these animals. Behavioural characteristics of SHR rats reflect an increased reactivity of their nervous system which may be connected with the mechanisms of the increase of arterial pressure.     

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.     

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.     

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.     

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.     

Functional and structural pattern of arterial responses in hereditary hypertriglyceridemic and spontaneously hypertensive rats in early stage of experimental hypertension

It has been shown that endothelium-derived nitric oxide (NO) plays an important role in regulation of vascular tone in the prenatal and early postnatal period. The aim of this paper was to determine the reactivity and accompanying structural changes in thoracic aorta from 4-week-old spontaneously hypertensive rats (SHR) and rats with hereditary hypertriglyceridemia (hHTG) in comparison with age-matched normotensive controls. For functional studies thoracic aorta was excised, cut into rings and mounted in organ baths for measurement of isometric contractile force. For morphological studies cardiovascular system of rats was perfused with glutaraldehyde fixative (at 100 mm Hg) via cannula placed in the left ventricle. Morphological changes of thoracic aorta were measured using light microscopy. Systolic blood pressure (SBP) in SHR (98+/-1 mm Hg) did not significantly differ from that of age-matched control rats (95+/-4 mm Hg), but was slightly increased in hHTG rats (110+/-2 mm Hg, P<0.05). Heart weight/body weight ratio was higher in SHR and hHTG rats than in control group indicating the hypertrophy of the heart in both models of hypertension. Endothelium-dependent relaxation of aorta induced by acetylcholine was preserved in all groups and did not differ from that in control normotensive rats. The maximal isometric contraction of thoracic aorta to noradrenaline (NA) was reduced in hypertensive groups and the concentration-response curves to NA were shifted to the right indicating increased sensitivity of smooth muscle to NA. The values of wall thickness and cross sectional area as well as inner diameter of thoracic aorta in SHR and hHTG rats were significantly decreased in comparison to control groups. Endothelial dysfunction seems to be absent in all young rats before development of hypertension. In conclusion, our observations indicate that in early stage of experimental hypertension NO-dependent relaxation is preserved so that putative impairment of this function provides no significant pathogenic contribution to the onset of hypertension in these two experimental models.     

Somatosympathetic reflex in rats with various models of arterial hypertension

Spontaneous and reflex activities of sympathetic nerve were compared in animals with arterial hypertension of different aetiology. Reflex discharges elicited by single-shock stimulation of afferent fibres were recorded. In acute experiences on anaesthetized rats with renovascular and spontaneous (SHR) model of arterial hypertension, electric basal and evoked activity (somatosympathetic reflex) in cervical sympathetic trunk were recorded. It is shown, that the spontaneous electric activity in sympathetic nerve of hypertensive rats is larger than spontaneous activity of normotensive control animals. The somatosympathetic reflex in hypertensive rats differs from that of control animals. In rats with renovascular model of hypertension, the reflex magnitude is reduced, and in the SHR the reflex is increased. Time characteristics of the reflex in hypertensive rats differed among them. It is suggested that functional activities of the brain stem in rats with different arterial hypertension model are unequal.     

Disruption of latent inhibition in ISIAH rats with stress-sensitive arterial hypertension

Latent inhibition phenomenon is used in the study of processes of selective attention in the context reinforcing training. The purpose of this study was a comparative analysis of the ability to ignore irrelevant stimuli in hypertensive ISIAH rats and normotensive Wistar rats with different psychoemotional statuses. Latent inhibition was formed in the passive and active avoidance tasks the development of which was preceded by repeated presentation (pre-exposition) conditioned stimulus without reinforcement. In ISIAH rats, disruption of latent inhibition in both behavioural tasks was observed as compared with Wistar rats. These data suggest that the deficit of selection information in ISIAH rats is caused by congenital weakness of internal inhibition in the adaptation to anxiogenic stimuli.     

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.     

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.     

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.     

Na,K-ATPase in kidneys of rats with hereditary hypertension induced by stress]

It has been found that Na, K-ATP-ase activity in microsomal fraction obtained from the medullar layer of kidneys of stress-sensitive hypertensive rats (SSHR) which were subjected to stress effects is lower by 20-40% than that in the Wistar rats. In hypertensive animals the stress (30-min immobilization) has led to a considerable increase in blood tension. Values I50 for ouabain and dependence of activity on the ratio of Na and K ions in the medium are similar in animals of both lines subjected to the stress. There are also no considerable differences in the protein composition of microsomal fraction from kidneys of rats of both lines. The effects which increase permeability of vesicules (channel-forming agent alamecytin, lubrol WX, freezing-thawing) activate Na,K-ATP-ase in the preparation from the kidneys of rats of the both lines. Under maximum activation there is a removal of differences in activity of the enzyme obtained from the tissues of the SSHR and Wistar animals after the stress action. Blood serum of SSHR rats after the stress inhibits purified Na,K-ATP-ase to the greater extent than the Wistar rat blood serum after the same effect. It is supposed that differences in Na,K-ATP-ase activity in microsomal fraction from the kidneys of rats of the above lines are stipulated by the differences in the "latent" ATP-ase activity.     

Local characteristics and interrelations between glands and lymphoid conglomerations in the esophageal wall

Proper glands in 248 total preparations and lymphoid accumulations in 112 preparations have been investigated macro-microscopically in the human oesophageal preparations at various age. The organs have been obtained from 152 corpses of persons died from the death by violence and having no pathological changes in the organs of digestive and immune systems. The lymphoid tissue in the oesophageal wall is presented as accumulations of cells (prenodules++) and as diffusely scattered immune-competent cells. The glands and lymphoid accumulations are oriented as longitudinal rows. The lymphoid tissue accumulations are situated near to the glandular ducts, because the latter can serve as pathways for penetrating antigenic material into the organ's wall. The amount of the glands is maximal mature and elderly age, and that of lymphoid accumulations--at the second childhood. The dimensions of the gland body increase in the cranio-caudal direction, while the lymphoid accumulations, just the reverse, have their maximal dimensions in the upper third of the oesophagus. The gland bodies in places of the organ's anatomical narrowings in the section have more alveoles and are situated nearer to the covering epithelium than the glands in the neighbouring areas of the wall.     

Renal and endocrine changes in rats with inherited stress-induced arterial hypertension (ISIAH)

Hypertensive inbred rats (ISIAH; inherited stress-induced arterial hypertension) present with baseline hypertension (>170 mmHg in adult rats), but attain substantially higher values upon mild emotional stress. We aimed to characterize key parameters related to hypertension in ISIAH. Kidneys, adrenals, and systemic endocrine parameters were studied in ISIAH of different ages and compared to normotensive Wistar albino Glaxo (WAG) rats. Native organs were obtained for Western and PCR analysis. Perfusion-fixed organs were prepared for histopathology and quantitative histochemistry. Plasma renin and adrenal hormones were measured. Renal morphology was unaltered in ISIAH. The hypothalamic-pituitary-adrenocortical (HPA) axis was constitutively upregulated with enlarged adrenal cortices and enhanced plasma corticosterone levels. Plasma renin activity was not different between groups, whereas aldosterone levels were in part reduced. Juxtaglomerular NO synthase type 1, cyclooxygenase type 2, and renin expression were significantly reduced, whereas tubular gene products related to sodium transport (bumetanide-sensitive Na, K, 2Cl cotransporter type 2; thiazide-sensitive Na, Cl cotransporter; epithelial Na channel-α; 11β-hydroxysteroid dehydrogenase type 2) were increased. These data suggest enhanced volume conservation by the kidney. Our data define ISIAH as an attractive model for the renal components determining salt and water homeostasis in hypertension. The specific condition of a basally stimulated HPA axis is highlighted, including the option to study effects superimposed by emotional stress.