Inhibition of secretory activity of atrial myocytes in hypertensive rats after losartan treatment.

Male ISIAH rats with inherited stress-induced arterial hypertension (BP 174.0 ± 1.3 mm Hg) received antagonist of angiotensin II receptors losartan in a dose of 10 mg/kg/day for 16 days. Ultrastructural study of the right atrium showed signs of dramatic and pronounced inhibition of synthesis of the natriuretic peptides (changes in the composition of secretory granules and decrease in their population density and size) the atrial myocytes against the background of persistent BP decrease in hypertensive rats to 142.0 ± 4.2 mm Hg. We concluded that myoendocrine cells in rats with stable hypertension retain ability to respond adequately to distention of the atria with blood.

Structural characteristics of renomedullary interstitial cells of hypertensive ISIAH rats.

The structural characteristics of the renal medulla and its interstitial cells were studied in hypertensive ISIAH rats (in comparison with normotensive WAG rats) in order to clear out the role of the renomedullary interstitial cells in the mechanisms of AP regulation. Morphometric electron microscopic analysis and immunohistochemical studies in ISIAH rats detected the initial signs of the renomedullary sclerosis. The renomedullary interstitial cells of ISIAH rats were characterized by higher numerical density and were larger in size, with a higher volumic share of their secretory granules. These structural features of the studied cells were regarded as signs of their more intense functional activity aimed at hypertension suppression.

Chromogranin location in the adrenal glands of ISIAH rats.

Comparative immunohistochemical and electron microscopic study of the adrenals from hypertensive ISIAH rats and normotensive WAG rats (control) showed a more intense reaction to chromogranin A in the ISIAH adrenal in comparison with the control. Electron microscopy and morphometric analysis showed high volume and numerical densities of the secretory granules in chromaffin cells of hypertensive rats. The results indicate stimulation of the adrenal medullary substance in ISIAH rats. Presumably, intensive accumulation of chromogranin A and secretory granules in chromaffin cells of hypertensive rats reflects a certain imbalance of chromogranin A and catecholamines biogenesis, this, in turn, leading to stable stimulation of the sympathoadrenal component and higher stress sensitivity of these animals.

Cardiac natriuretic peptides and development of hereditary hypertension in rats.

Ultrastructure of the right atrial cardiomyocytes of suckling ISIAH rats was studied to clarify the role of cardiac natriuretic peptides in hypertension development during the period when blood pressure is not yet elevated. Cardiomyocytes diameter was significantly greater, Golgi complex was more developed, and granules in the sarcoplasm were more abundant in ISIAH rats as soon as on postnatal day 12 in comparison with age-matched normotensive animals. The smaller diameter of granules and their qualitative composition (ratio of forming, mature, and dissolving forms) attest to active synthesis and release of secretory product. In 21-day-old ISIAH rats, granule size and qualitative composition reflected increased accumulation of hormones in the cells. Thus, morphological features of increased production of natriuretic peptides in the right atrial myocytes were revealed in rats during the first postnatal month before manifestation of hereditary hypertension.

Aldosterone and stress-dependent arterial hypertension.

Secretory activity of the adrenal cortex and hormonal reaction to emotional stress were examined in normotensive WAG and hypertensive ISIAH rats. Under nembutal narcosis (surgical stage), secretion of corticosteroid hormones and hormonal reaction to acute stress in hypertensive rats were enhanced. In these rats, the stress-induced elevation of aldosterone secretion was most pronounced, which indicates an important contribution of this hormone to the pathogenesis of stress-dependent arterial hypertension.

Structural characteristics of renal glomerular system in ISIAH rats under conditions of chronic stress and preventive hypotensive drug therapy.

The effects of chronic stress on the structure and function of the renal glomerular system were studied in hypertensive ISIAH rats treated with hypotensive drugs during the early ontogeny. The morphometric parameters of the renal glomerular system, characteristic of each of the experimental animal groups treated by enalapril, losartan, or terazosin in early age virtually did not change under conditions of stress exposure. These results indicate a persistent delayed nephroprotective effect of these drugs.

Delayed effects of hypotensive drugs on structural characteristics of the renal glomerular system in hypertensive NISAG rats.

Comparative morphometrical study of the renal glomerular system was carried out in hypertensive NISAG rats treated with hypotensive drugs during the prepubertal period. Blockade of the renin-angiotensin system with enalapril or losartan during the critical period of ontogeny (the 2nd month of life) produced a long-term hypotensive and renoprotective effect. Treatment with alpha-adrenoblocker terazosin during this period of ontogeny produced a less pronounced hypotensive effect, though with renoprotection. Corinfar (Ca2+ channel blocker) was least effective.

Functional activity of the sympathoadrenal system in hypertensive NISAG rats.

NISAG rats with stress-induced arterial hypertension are characterized by hyperactivity of the sympathoadrenal system under rest conditions and during stress exposure.

Delayed effects of enalapril on structural characteristics of the glomerular apparatus in the kidneys of NISAG rats.

Structural characteristics of renal glomeruli were studied in adult hypertensive NISAG rats (hereditary stress-induced hypertension) receiving antihypertensive drug enalapril, an inhibitor of angiotensin-converting enzyme, on days 28-58 of life. Treatment with enalapril (25 mg/kg perorally) in the early period of postnatal ontogeny produced delayed hypotensive and nephroprotective effects.

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.

Structural characteristics of cardiomyocytes in the right atrium of NISAG rats.

Electron microscopy and stereomorphometric analysis of hypertrophic cardiomyocytes in the right atrium of NISAG rats revealed signs of activation of biosynthetic processes: increased relative volume of euchromatin (compared to Wistar rats), high density of nuclear pores, presence of large numerous Golgi complexes, and well-developed endoplasmic reticulum. The numerical density of secretory granules in the cytoplasm of cardiomyocytes in NISAG rats significantly surpassed that in Wistar rats. However, these granules in NISAG rats were smaller than in Wistar rats. The presence of numerous secretory granules and increased ratio of forming and dissolving structures suggest that this pool is characterized by high turnover rate, i.e., intensive synthesis and rapid elimination (consumption) of natriuretic peptide. Hypertrophy and hyperactivity of endocrine function in atrial cardiomyocytes of NISAG rats can be considered as a compensatory reaction to hypertension.

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.

Effect of chronic stress during neonatal ontogeny on structural organization of the adrenal gland in hypertensive NISAG rats.

Structural organization of the adrenal gland was studied in 3-week- and 6-month-old hypertensive NISAG rats subjected to daily handling (10-min separation from mothers) on postnatal days 1-21. Neonatal handling reduces the stress-induced blood pressure rise in adult NISAG rats and modulates the structure of the adrenal cortex and medulla.

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.

Pathophysiological aspects of experimental myocardial infarction during arterial hypertension.

We compared the results of clinical and experimental studies of endocrine parameters in patients with myocardial infarction and arterial hypertension and NISAG rats with hereditary stress-induced arterial hypertension during experimental myocardial infarction. Changes in the content of corticosterone, aldosterone, insulin, triiodothyronine, and thyroxin were similar in animals and patients with myocardial infarction and arterial hypertension. The disadaptive course of myocardial infarction against the background of arterial hypertension can be explained by reduced compensatory capacity of the myocardium.

Peculiarities of myocardial structure in rats with hereditary hypertension reared by normotensive females.

Morphometric analysis revealed no signs of myocardial hypertrophy at the tissue and ultrastructural levels in 3-week-old NISAG rat pups reared by normotensive Wistar females. The severity of myocardial hypertrophy in these animals aging 6 months was similar to that in NISAG rats reared by natural mothers. However, raising conditions during the early ontogeny form compensatory structural changes in the myocardium of rats with genetically determined hypertension.

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.

Development of hypertensive status in NISAG rats reared by normotensive Wistar rats.

Parameters of the cardiovascular system and the content of corticosterone, thyrotrophin, thyroxin, and triiodothyronine in the plasma, and norepinephrine in the myocardium were determined in male NISAG rats (hereditary stress-induced arterial hypertension) reared by normotensive Wistar rats. Cross-rearing of hypertensive rat pups by normotensive females attenuated arterial hypertension with a tendency to normalization of the examined parameters. This confirms the possibility of modifying hypertensive phenotype by changing the conditions of the early postnatal development.

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.

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

Plasma, lymph and myocardial Fe(2+) contents and blood antioxidant activity were studied in hypertensive NISAG and normotensive Wistar rats with experimental myocardial infarction. In hypertensive rats, iron levels in plasma, lymph and myocardial tissue were increased throughout the experiment. In both strains iron content in the plasma during experimental myocardial infarction negatively correlated with blood antioxidant activity. In hypertensive NISAG rats this correlation persisted also during recovery. This attests to prooxidant effect of Fe(2+) aggravating the course of myocardial infarction in NISAG rats.