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It is well known now that atrial cardiomyocytes carry out both contractile and endocrine activities--they synthesize, accumulate in specific secretory granules and release the natriuretic peptides. The main physiological effects of natriuretic peptides are antagonistic to the renin-angiotensin-aldostrol system, but their role in the development of hypertension is still disputable. The aim of this investigation is to estimate using electron microscopy the secretory activities of atrial myoendocrine cells in rats with inherited stress-induced arterial hypertension (ISIAH stain). It has been shown that myoendocrine cells in the ISIAH rats with arterial pressure about 180 mm Hg reveal morphological features of increased synthesis, extra accumulation and release of natriuretic peptides compared with normotensive control rats. In the ISIAH rats treated with losartan (angiotensin II receptor blocker) and therefore having a sustained decrease in arterial pressure to 140 mm Hg, changes in granular pool composition, reduction of the number and diameter of the secretory granules, reduction of Golgi complexes, and increased intracellular degradation of secretory stores were found in the myoendocrine cells. At the same time the marked capillary hyperemia and interstitial edema in the myocardium were observed. Thus, in rats with severe inherited hypertension, the secretory activity of heart myoendocrine cells is sharply increased and directly depends on the arterial blood pressure level. This proves that natriuretic peptides actively participate in the regulation of hemodynamics during with cardiovascular pathology.

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The peculiarities of cardiac natriuretic peptide secretion have been investigated during ontogenesis using the hypertonic disease model in ISIAH rat line (with inherited stress induced arterial hypertension). The qualitative and quantitative ultrastructural investigations of right atrium myocardium revealed that the cardiac hormonal synthetic and secretory activities in ISIAH rats are higher as compared with normotensive even-aged rats from control group. Secretory hyperactivity of atrial myocytes in ISIAH rats during early ontogeny precedes the manifestations of hereditary hypertension. Natriuretic peptides present the hypotensive circuit of hemodynamic regulation during the whole ontogeny and the complementary chain in hypertension development.

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Treatment with different types of antihypertensive drugs during second month age has not prevented development of arterial hypertension and myocardial hypertrophy in the adult rats with inherited stress-induced arterial hypertension. At 6 months of age, the 11% attenuation of basal blood pressure has beet achieved only in the rats treated with angiotensin-converting enzyme inhibitor enalapril. Nevertheless, they expressed the most pronounced left ventricular hypertrophy. The unfavorable tissue and ultrastructural abnormalities were revealed in the myocardium of the rats which received the alpha1-adrenoceptor blocker terazosin. The delayed effects of losartan (angionetsin II receptor antagonist) and corinfar (calcium channel antagonist) on the myocardial structure were inessential.

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In rats with inherited stress-induced arterial hypertension (ISIAH strain), myocardium, adrenal gland, and renal glomerular apparatus were studied at different periods of postnatal ontogenesis (3 weeks and 6 months) to assess the influence of the changed conditions of nursing on the development of a hypertensive status and structural-functional characteristics of target organs. It was demonstrated that nursing of rats by foster normotensive Wistar females exerted a modulating influence upon the realization of stress-determined program of arterial hypertension development, seemingly delaying it and alleviating the negative consequences in respect to the target organs, through increased effectiveness of recruitment of adaptive-compensatory organism reserves, however, on the whole, it did not interrupt this program.

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The comparative investigation of the adrenal structure in two groups of rats of Inherited Stress-Induced Arterial Hypertension (ISIAH) strain was conducted. The animals of the first group were nursed by normotensive Wistar rats, while those of the second (control) group were reared by their own mothers. The volume of the adrenal medulla in rats of the first group was found to exceed that in the second group. In the adrenal zona glomerulosa and zona fasciculata of 3-week-old rats of the first group parenchymal-stromal ratio and the average volume of adrenocorticocytes were lower than those in the animals of the second group. This was accompanied by a decrease in mitochondrial volume density and accumulation of lipid droplets in the cytoplasm, indicating a reduction of hormone-producing activity of endocrinocytes in the animals the first group as compared to controls. By 6 month of age, arterial pressure and quantitative parameters of adrenal medulla and cortex in the animals the first group were..... as compared to those in the second group. It is suggested that the nursing of ISIAH rat pups by normotensive Wistar dams had modulating effect on the adrenal structure and therefore on arterial hypertension development.

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Comparative electron microscopic study of glomerular apparatus was performed in 6-month old Wistar rats and in rat strain with inherited stress-induced arterial hypertension (ISIAH). It was shown that this stage of hypertensive status formation was characterized by hypertrophy of renal corpuscles, accompanied by structural changes of all their cellular and noncellular components. These included abrupt capillary constriction or dilation, endothelial flattening, podocyte hypertrophy and flattening of their cytopodia, thickening of basal lamina, mesangial volume expansion and increase in the number of intercapillary processes of mesangial cells. Complex of these signs suggests a disturbance of glomerular capillary blood circulation and a functional podocyte stress, compensating these microcirculatory disturbances. Changes in basal membranes and mesangium are indicative of not only increase in filtration barrier functional load, but also of initial stages of glomerular sclerosis.

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The comparative investigation of the adrenal cortex in hypertensive (INHERITED STRESS-INDUCED ARTERIAL HYPERTENSION--ISIAH) and normotensive strain (Wistar) 12-months age rats was performed. The structural signs such as the lowering of the mitochondria volume involved in steroid synthesis in showed more notable age-related reduction of steroidogenesis in the adrenal glomerular and fascicular zones and in the ISIAH rats. The lowering of the cell steroidogenesis was compensated by the adrenal glomerular and fascicular zones and hypertrophy as a result the adrenocorticocytes hyperplasia. At the same time the more considerable sclerotic changes of the adrenal cortex periendothelial space were demonstrated in the ISIAH rats. The results obtained give evidence that reducing potential of compensatory possibilities of the adrenal cortex of the ISIAH rats in the late postnatal ontogenesis period cause high probability of adaptative-compensatory mechanisms failure and pathological process aggravation in these animals.

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Studies of lipid metabolites in the plasma and lymph of rats with hereditary arterial hypertension induced by stress (HAHIS) showed decreased plasma and lymph pool of total cholesterol (TC) in comparison with normotensive Wistar rats. In HAHIS animals, TC concentration in the lymph was lower than in the plasma. The concentrations of triglycerides and free fatty acids in the plasma and lymph of hypertensive animals were virtually the same and higher than in normotensive ones. Plasma concentration of malonic dialdehyde (MDA) in HAHIS rats was the same as in Wistar rats, while the lymph concentration of MDA was higher than in Wistar rats. The detected lipid metabolism characteristics reflect its genotypical and phenotypical rearrangement and are a component of the "metabolic syndrome", detected in patients with essential hypertension and animals with spontaneous arterial hypertension.

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Morphological changes of myocardium were demonstrated in normotensive Wistar rats and in rats with inherited stress-induced arterial hypertension 1, 7 and 30 days following adrenaline induced damage. In acute period contracture damage to cardiomyocytes was more pronounced in Wistar rats. Death of the fraction of cardiomyocytes is compensated by hypertrophy of the surviving cells already by d 7. In hypertensive rats' hypertrophied myocardium on d 1 microcirculatory bed is more impaired, while regenerative processes in cardiomyocytes are delayed and defective, which leads to dystrophy and degeneration by the end of the experiment. It is concluded that the course and prognosis of myocardial metabolic injury is determined by its initial state and potential compensatory resources.

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Maternal arterial blood pressure (ABP) of hypertensive (ISIAH) and normotensive (Wistar) rats rearing their natural litter or litter of opposite strain, was assessed when the pups were 1.5-, 3- and 4-month old and compared with the ABP of these rats prior to their mating. The ABP was increased in both breeds of rat strains for either cross-fostered or infostered pups. No ABP changes were observed in control rats.

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The morphological and functional consequences of epinephrine-induced myocardial infarction were studied in normo- (Wistar) and hypertensive (ISIAH) rats. After experimental myocardial infarction there was an irreversible transition to the "worn-out" stage or "plastic damage" to the myocardium. Thus, myocardial hibernation in ISIAH rats anticipates and determines the development of myocardial stunning, i.e., irreversible myocardial damage, whereas in the normotensive animals, the protective effect of hibernation is fully shown. The ontogenetic features of myocardial response of ISIAH rats to hypoxia promote transformation of adaptive hibernation and stunning to maladaptive pathological changes causing hypoxic alterations.

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Comparative morphometric examination of adrenal cortex was carried out in 3 wks HNCAI rats with inherited stress induced arterial hypertension and normotensive Wistar rats. Relative adrenal mass, volume of cortex and its glomerular zone in HNCAI rats exceeds appropriate values in Wistar rats. Increase of adrenocorticocytes due to hyperplasia of their ultrastructural components was found. In hypertensive rats adrenocorticocyte numerical density increase due to their hyperplasia was found in adrenal fasciculate zone in contrast to glomerular one. These structural organization peculiarities in 3 wks hypertensive rat adrenal cortex reflect their elevated functional activity and may determine genetically programmed increased organism responsiveness to stress that consequently provides the grounds for the hypertensive status formation in this rat line.

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Micronuclei of preimplantation embryos of the hypertensive rat strain with inherited spontaneously induced arterial hypertension (ISIAH) are studied. Also studied are the formation of micronuclei and other morphological changes in these embryos after freezing, cryoconservation, and consequent transplantation to Wistar recipient rats. Analysis of semithin sections demonstrates that the above procedures lead to the formation of micronuclei in most embryos, while the shape of nuclei changes in only some embryos. There is a tendency towards perinuclear location of organelles and inclusions and to the partial disappearance of polarity in the majority of blastomeres. We believe that the increase in the number of micronuclei can be associated with a certain selection of embryos during cryoconservation and transplantation.

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