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Accumulation and release of atrial and brain natriuretic peptides (ANP and BNP) in right atrial cardiac muscle cells has been investigated in rats after 60 minutes and 60 days after the reperfusion start. The total ischemia was simulated by the method of V. G. Korpachev. Immunocytochemical localization of peptides in cardiomyocytes was performed in ultrathin sections using polyclonal antibodies. The intensity of accumulation/excretion of ANP and BNP were analyzed by the method of counting the number of granules (A- and B-types) with immunoreactive labels in 38 x 38 mkm2 visual fields in transmission electron microscope Morgagni 268D (FEI). The results were assessed using Mann-Whitney U-test (p < 0.05). After 60 minutes and 60 days post-reperfusion period, we detected an increase in the synthesis and release of ANP and BNP. The reaction of BNP was more pronounced than ANP. This is due to the fact that ANP is the main hormone of the natriuretic peptide system involved in the regulation of blood pressure in normal conditions, while BNP is the principal regulator of pressure in cardiovascular pathology.

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.

A qualitative and quantitative ultrastructural study of right atrial cardiomyocytes in WAG (normotensive control) and ISIAH (inherited stress-induced arterial hypertension) rats of different age (on day 18 of embryogenesis, on days 12 and 21 after birth, and at an age of 6 and 13 months) was performed. It was shown that, in embryos with an as yet incomplete atrial morphogenesis, secretory granules containing natriuretic peptides are actively formed, accumulated, and dissolved. In postnatal ontogeny, the secretory product is accumulated in atrial cells. In all ontogeny stages studied, the numerical density of secretory granules in the myoendocrine cells of hypertensive rats is greater and the qualitative composition of these granules is more diverse than in the control. It was established that, in atrial myocytes of ISIAH rats, the morphological signs of natriuretic peptide hypersecretion precede the development of genetically programmed high blood pressure. In adult hypertensive rats, hypertrophic and degenerative changes in myocytes are accompanied by excessive accumulation of secretory granules, some of which undergo intracellular degradation.

Completion of the process of maturation of spermatozoa (capacitation) occurs in the female genital tract. As a result, spermatozoa acquire hypermobility and the capability for the acrosomal reaction, which determine their fertility. There exist data that participating in these processes are the adenylyl cyclase and guanylyl cyclase signaling systems that are present in human and mammalian spermatozoa. The goal of the present work to characterize these systems in the human ejaculate spermatozoa (ES) and in the human fertile spermatozoa (FS) isolated by the density gradient centrifugation. In the FS homogenate the basal activity of adenylyl cyclase (AC) activity was significantly higher that in ES: 47 +/- 5 vs 28 +/- 3 pmol cAMP/min per mg of protein, respectively. At the same time, the AC-stimulating effects of non-hormonal activators of AC forms (NaHCO3, Mn2+, forskolin, and non-hydrolysable GTP analogue - GppNHp) were lower as compared with ES. The AC activity in ES were stimulated by isoproterenol, serotonin, PACAP-38, and, to the letter degree, by noradrenalin and adenosine. Among the AC-inhibiting hormones, adenosine alone decreased the enzyme activity. In FS, on the contrary, the AC-inhibiting effects of adenosine, noradrenaline, and serotonin were clearly expressed, whereas the stimulatory effects of these hormones were attenuated or absent. The basal activity of guanylyl cyclase (GC) in the ES and FS homogenates amounted to 27 +/- 3 and to 21 +/- 2 pmol cGMP for 1 min per 1 mg protein, respectively, and was significantly increased in the presence of 10 mM Mn2+. The GC-stimulating effects of natriuretic peptides - atrial natriuretic peptide (ANP) and the C-type natriuretic peptide (CNP)--activators of the GC receptor forms, were in ES significantly higher than in FS, the ANP effect being more pronounced as compared with CNP. The obtained data indicate multiplicity of the cAMP- and cGMP-dependent signal cascades regulating fertility of human spermatozoa. It has been established that sensitivity of AC and GC to hormones in the total ES pool and in the supermobile FS fraction isolated by centrifugation differs essentially, which is to be taken into account when using FS for auxiliary reproductive technologies.

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.

The wide experience in the ultrastructural study of myoendocrine cells of different animal species in normal and experimental conditions allows us to choose the optimal methodology that gives the most complete information about the state of intracellular secretory apparatus. It is revealed that the combined set of atrial myoendocrine cell qualitative and quantitative parameters allows defining the natriuretic regulatory system status, as well as it's acute and chronic responses to hemodynamic changes. The information value of such approach is illustrated by examples of the ontogenetic investigation in two rat lines: with normal arterial blood pressure and with inherited stress-induced arterial hypertension. The proposed methodology is quite sensitive and descriptive; so it is of high importance due to insufficiency of other universal, specific, and accurate methods for cardiac natriuretic peptides investigation.

The ultrastructural and stereomorphometrical study of the right atrium of chick embryos at the 14th day of incubation has shown the cardiomyocytes to divide by mitosis and to be at different stages of differentiation. In the cytoplasm of some muscle cells we detected secretory granules that by their sizes and morphology can be classified into the forming, mature, and dissolved forms. By the 18th day of incubation most cardiomyocytes are already differentiated, and the number of secretory granules in them rises. Under conditions of hypoxia, after 3 days, in myoendocrine cells there are noted signs of accelerated release of the peptides synthesized earlier and accumulated in granules, while after one week - of enhancement of their synthesis. It can be concluded that in chick embryos, beginning from at least the 14th incubation day, the system of natriuretic heart peptides takes part in regulation of hemodynamics and of water-salt balance and responds to hypoxia.

Interventricular septum myocardium was studied in 40 patients with obstructive hypertrophic cardiomyopathy. Immunohistochemical assay revealed c-kit-positive resident cardiac stem cells in 82.5% patients. The content of the connective tissue and myofibrillar disarray zones and the degree of cardiomyocyte hypertrophy and myolysis were determined. In 30% cases, cardiomyocytes containing atrial natriuretic peptide were detected in the interventricular septum myocardium. The data were compared with clinical and functional parameters of patients. It was found that cardiac stem cells are present in patients, whose myocardium was characterized by increased density of the connective tissue, hypertrophy of mature cardiomyocytes, medium degree of myolysis in them, and accumulation of natriuretic peptide, a cardiac failure marker, in cardiomyocytes.

A method for the estimation of severity of chronic cardiac failure (CCF) based on the quantitative evaluation of the regulatory and adaptive status (RAS) of the organism. Patients with FC I-III HCF concomitant with grade I-III hypertensive disease and/or coronary heart disease underwent cardiorespiratory synchronism test for the quantitative estimation of RAS (6 min walk), echocardiography, treadmill measuring maximum oxygen consumption (VO2max), measurement of plasma N-terminal precursor of brain natriuretic peptide. The lowering of RAS was especially pronounced when HCF FC changed from I to III, in agreement with results of traditional instrumental and laboratory tests. Specifically, left ventricle systolic and diastolic function was impaired, tolerance of physical exercise decreased while neurohumoral regulation was activated. There was positive correlation between RAS indices at HCF CF I and II for left ventricular ejection fraction, maximum physical load, VO2max and negative correlation for N-terminal precursor of brain natriuretic hormone. At HCF FC II and III, positive correlation was documented for left ventricular ejection fraction, maximum physical load, VO2max and negative correlation for the N-terminal precursor of brain natriuretic hormone. It means that the qualitative estimate of RAS obtained in the cardiorespiratory synchronism test can be used to assess severity of HCF in patients with hypertensive disease and/or coronary heart disease.

Participation of kidney in maintenance of constancy of parameters of the organism internal medium is connected with formation in it of physiologically active substances. They are components of systems of regulation of water-salt balance, arterial pressure, blood coagulation, erythropoiesis. Mechanisms of normalization by kidney of concentration of hormones in blood and of modulation of action of hormones are analyzed.

The system of cardiac natriuretic peptides (NP) is a very important factor opposing the effects of the rennin-angiotensin-aldosterone system (RAAS), sympathoadrenal system and vasopressin to reduce blood pressure. In the present study, we analyzed the release of atrial and brain natriuretic peptides in the myocytes of the right atrium in rats by the quantitative morphometric method using double immunocytochemical labeling of atrial granules comprising NP in vasorenal hypertension induced by the renal artery ligation. The decrease in the total amount of secretory granules in atrium myocytes by 18% was detected on the 30th day after the operation. The number of the A-type granules was reduced by 53%, and the number of B-type granules was increased by 64% in comparison with the intact animals. Our data indicate activation of NP secretion in vasorenal hypertension. The results suggest that high arterial pressure might be explained by reduced expression of NP receptors in this pathology.

Electron microscopic observations of the lymph hearts of tadpoles and yearling frogs of Rana temporaria showed that mast cells (MCs) were present not only between muscle fibers (population of resident MCs), but in the cavities of lymph heart (population of circulating MCs), too. There were some differences in the ultrastructure of the resident MCs at each studied stage of larval development. The first recognizable MCs were revealed in the lymph hearts at premetamorphosis (stages 39-41). MCs presented as mononuclear relatively small and slightly elongated cells with a few immature secretory granules and numerous free ribosomes, polysomes and short cisternae of rough endoplasmic reticulum (RER) in the cytoplasm. Chromatin of their nuclei was poorly condensed; the Golgi apparatus was moderately developed. At pro-metamorphosis (stages 44-45), we revealed MCs at different levels of their differentiation. Some MCs demonstrated an active process of granulogenesis in their cytoplasm. Among densely packed cytoplasmic organelles, immature secretory granules were closely associated with cisternae of RER and free ribosomes. Other MCs appeared as more differentiated cells. They were characterized by a predominantly heterochromatic nuclei and cytoplasm filled with polymorphic and heterogeneous granules. MCs also showed a reduction in the number of free ribosomes and cisternae of RER in the cytoplasm. On the contrary, the Golgi apparatus was well developed. Stacks of Golgi cisternae, detaching vacuoles, and progranules occupied the perinuclear region. The majority of the outlines above ultrastructural features of differentiated MCs were typical for MCs of yearling frogs. At metamorphic climax (stages 52-53), MCs often tightly contacted with macrophages. We did not reveal apoptotic MCs. However, some MCs exhibited morphological features typical for programmed necrosis-like death, which was characterized by mitochondria swelling, dilatation of cisternae of RER and nuclear envelope, plasma membrane rupture and subsequent loss of intracellular contents. Electron microscopical immunocytochemistry revealed the localization of atrial natriuretic peptide (ANP), substance S (SP) and heat shock protein (Hsp70) in the secretory granules of the resident and circulating MCs at different stages of tadpole development and in yearling frogs.

It is known that many heart diseases are accompanied by a significant increase in the level of atrial natriuretic peptide (ANP), a regulator of cardiovascular homeostasis, in the pericardial fluid. Cellular sources of ANP in pericardial cavity remain uncertain. By EM immunocytochemistry, we have examined the presence and localization of ANP in rat and human pericardium. ANP-immunoreactive material was revealed in granules of mast cells (MCs) situated in connective tissue of the pericardium. MCs have an oval form and measure about 6.5 x 12.5 and 9.1 x 13.6 microm in the rat and human pericardium, respectively. Density of MC population makes up about 50 and 10 cells/mm2 in the rat and human pericardium, respectively. Our data suggest possible participation of the pericardial MCs in endocrine function of pericardium and in control of the ANP level in pericardial cavity.

Three types of cells circulate in haemolymph of the crayfish Astacus astacus: agranular haemocytes (HCs I), small-granule haemocytes (HCs II) and large-granule haemocytes (HCs III). Their proliferation, differentiation and function remain poorly understood. By means of light and electron microscopic autoradiography using [3H]-thymidine, we have revealed that only HCs I are capable of DNA synthesis and mitosis whereas HCs II and HCs III are replicatively inactive. To determine whether the HCs I are proliferating progenitor cells for the granular HCs, we have analyzed autographs of HC population in 1, 2, 7 and 21 days after a single [3H]-thymidine administration. Contrary to the expectation, we have failed to find labeled HCs II and HCs III. These findings raise doubts on the capacity of the HCs I to differentiate into two other types of HCs. By autoradiography using 3H-uridine, it has been detected that intensity of the RNA synthesis was the greatest in HCs I and less by a factor of two and four in HCs II and HCs III, respectively. Additionally, by EM immunocytochemistry, ANP-like immunoreactivity was revealed in the large granules of the HCs III. We assume that availability of ANP in secretory granules extends the possible functions of the crayfish HCs and suggests their participation in regulation of water-salt balance and immune responses.

At present there exists a limited understanding of mechanisms of differentiation and specialization of cardiac conduction system in mammals. For characterization of its development and differentiation on early stages we used as experimental model murine embryonic stem cells expressing enhanced green fluorescent protein (eGFP) under transcriptional control of human atrial natriuretic peptide (ANP) as promoter. Cardiac nature of ANP-eGFP was confirmed by immuno staining with antibodies to troponin I and a-actinin. In ANP- eGFP expressing embryonic stem cells it is possible to distinguish subpopulation of spindle-shaped pacemaker cells capable to higher frequency of spontaneous contractions, velocity of activation and amplitude compared with those of triangular and polygonal atrial-like cardiomyocytes. These results show that expression of ANP-eGFP cells allows to identify pacemaker cells among embryonic stem cells by their morphological and electrophysiological properties.

Chromogranin A (CgA) is a member of the granin family of acidic proteins that present in the secretory granules (SGs) of many endocrine, neuroendocrine and neuronal cells. Atrial natriuretic peptide (ANP)-storing SGs in atrial cardiomyocytes of rat heart also contain CgA. Cardiosuppressive effect of CgA-derived peptides (vasostatins) on in vitro isolated and perfused working frog and rat hearts has been shown under both basal conditions and beta-adrenergic stimulation. More recently it has been revealed that rat heart produces and processes CgA-derived vasostatin-containing peptides. Until now nothing has been known about the presence of CgA in an amphibian heart. We have investigated the subcellular localization of CgA in atrial myocytes of adult frog Rana temporaria heart using ultraimmunocytochemical method. Immunocytochemical staining of the frog atrial tissue for CgA and ANP has shown that out of three morphologically different types (A, B and D) of specific cytoplasmic granules (SCGs) present in myocytes only two (A and B)--large (120-200 nm in diameter) granules with more and with less electron dense core--exhibit immunoreactivity (IR) to these two antigens. The third type (D) of granules (80-100 nm in diameter) are small membrane bound granules characterized by highly electron dense core surrounded with a thin halo. These granules revealed negative reaction on immunostaining for both CgA and ANP. The presence of CgA- and ANP-IR in the same SCGs in frog atrial myocytes is consistent with the endocrine nature of these granules. Taking into account our and literature data we propose that CgA present in frog atrial cardiomyocite SCGs might be a precursor of vasostatin-containing peptides, as it takes place in rat heart. It is possible that these CgA-derived peptides together with ANP exert their regulatory function through the autocrine and/or paracrine mechanisms and play important cardioprotective role in frog heart under stress condition.

Aim: To study interrelation of main clinico-hemodynamic parameters and levels of natriuretic peptides (NUP) in patients with hypertrophic cardiomyopathy (HCMP)., Material and Methods: We measured concentrations of N-terminal fragments of precursors of plasma brain and atrial natriuretic peptides (NT-proBNP and NT-proANP) and conducted complex echocardiographical examination in 94 patients (mean age 42.3 +/- 133.8 years) with obstructive (n=43) and nonobstructive (n=51) HCMP., Results: Content of NUP did not depend on patients age, contractile function and dimensions of the left ventricle (LV), moderate and significant correlation between content of NT-proBNP, NT-proANP and type of ventricular filling (r=0.45 and 0.46, respectively), heart failure functional class (r=0.41 and 0.44, respectively), severity of LV hypertrophy (r=0.42 and 0.34, respectively), left atrial dimension (r=0.26 and 0.35, respectively), magnitude of pressure gradient in LV outflow tract (r=0.35 and 0.26, respectively). Degree of mitral regurgitation correlated significantly only with NT -proBNP level (r=0.34). The patients who eventually died (n=6) were characterized by higher plasma content of NUP., Conclusions: In patients with HCMP elevated plasma content of N-terminal precursors of brain and atrial natriuretic peptides are associated with severity of LV diastolic dysfunction and hypertrophy of LV as well as of hemodynamic and functional disturbances.

In this study, in the primary cell culture of human fetal cardiomyocytes proliferation of myocytes combines with their differentiation. The cells were isolated enzymatically from 19-22 week-old human fetuses and cultured for 14 days. DNA synthesis, ultrastructure and presence of atrial natriuretic peptide (ANP) were examined. In 7 day-old culture, the myocytes make about 60%, in 14 day-old culture--about 50%. Myocytes synthesize DNA and divide mitotically. After a 24 h incubation with 3H-thymidine in 7 day-old culture 1.8 +/- 0.5% of muscle and 25.2 +/- 11.7% of non-muscle cells are labeled, in 14 day-old culture--2.5 +/- 0.5 and 8.1 +/- 1.7% of cells are labeled, respectively. In 7 and 14 day-old cultures the degree of redifferentiation of contractile apparatus in myocytes varies from scattered actin and myosin filaments surrounded by ribosomes to differentiating myofibrils with distinct sarcomeres and Z-discs. Single electron-dense granules, morphologically similar to secretory atrial granules, display ANP-immunoreactivity. Thus, human fetal ventricular cardiomyocytes in cell culture proliferate, differentiate and synthesize ANP for 14 days; this is indicative of vitality of these cells.

In parallel with contraction, vertebrate cardiomyocytes perform endocrine function and produce natriuretic peptides (NP)--ANP and BNP--involved in cardiovascular homeostasis maintenance. ANP-like peptides have been reported also in hearts of some invertebrates, however, their cellular localization was not determined. By electron microscopical immunocytochemistry with polyclonal monospecific antibodies raised against ANP and protein A-gold technique, we have localized ANP-like immunoreactivity in granules within endothelial cells in the heart of the brachiopod Rhynchonella psittacea, the polychaete Arenicola marina, and the gastropod mollusc Achatina fulica--all being representatives of the major phylogenetic group Lophotrochozoa. ANP-like immunoreactivity was also revealed in one of 3 morphologically distinguishable types of granules in the snail heart granular cells. By electron microscopical autoradiography with the use of [3H]-thymidine, the ability for DNA synthesis was demonstrated in heart endothelial cells of the investigated animals. Forms of NP-system organization in hearts of Lophotrochozoa and Vertebrates, and close histogenetic relationships of endothelial and granular cells in the snail heart are discussed.

We determined the optimal conditions suitable for expanding cardiac cells in vitro for their future use in experimental transplantation into injured myocardium of adult animals. Ventricular cardiac cells were isolated enzymatically from 2-3 day-old rats and cultured at different cell densities within 5-7 days to 4 weeks. Mixed cultures of muscle and non-muscle cells were examined by light autoradiography, electron microscopy, and immunogold method. The best results were obtained at a density of 3 x 10(5) cells/ml in the medium, consisting of 90% DMEM and 10% fetal calf serum, during 5-7 days of cultivation. In such cultures myocytes made 62.5 +/- 7.9%. After a 24 h incubation with 3H-thymidine, 22.0 +/- 2.2% of myocytes were labeled. Muscle cells contact with each other and with non-muscle cells, contain myofibrils, contract and display atrial natriuretic peptide (ANP)-like immunoreactivity.

This literature review presents current information on mechanisms of realization and action of natriuretic peptides in heart failure and hypertension. Significant role in degradation of natriuretic peptides belongs to neutral endopeptidase. Basing on theoretical and experimental data novel class of drugs - inhibitors of neutral endopeptidase - has been developed. The paper contains discussion of first results of the use of drugs from this class for the treatment of chronic heart failure.

The review presents current data on production, release and reception of natriuretic peptides (NUP) with special focus on NUP effects on blood circulation, urination in arterial hypertension and cardiac failure; analyses interaction between NUP and renin-angiotensin-aldosterone system, effects of new drugs influencing these systems.

Monoamine oxidase (MAO) catalyzes the biological degradation of the neurotransmitters monoamines. The altered substrate specificity of MAO may be of pathogenic importance in some cases and MAO inhibitors showed a therapeutical effect in the experimental setting. Analyzing the efficacy of various compounds in inhibiting MAO A and B revealed new approaches to designing new-generation MAO inhibitors. Tribulin is a fraction of endogenous MAO inhibitors that are present in human and animal tissues and biological fluids. Isatin is an endogenous indole which was initially derived from a tribulin fraction. An investigation of the biological properties of tribulin revealed its heterogeneity and some chemical components were identified. It was shown that deficiency of tribulin components that selectively inhibited MAO A long with a larger number of molecules of this enzyme might be of great importance for the development of alcoholism. In addition to MAO inhibition, the physiological concentrations of isatin inhibited the receptor-binding of atrial natriuretic peptides and ANP-stimulated guanylate cyclase (GC). The sensitivity of ANP-GC to isatin might be allosterically regulated. Selective antagonists of natriuretic peptide receptors were found among isatin analogues which may be an effective pharmacological tool for further studies of the role of natriuretic peptides in the body.

Echocardioscopy in M- and B-modes with measurement of routine parameters of central hemodynamics and thickness of carotid intimal-medial segment as well as radioimmunoassay of plasma concentrations of atrial natriuretic peptide (ANUP) were performed in 159 patients aged 42-63 years (17 healthy subjects and 142 patients with cardiac failure associated with ischemic heart disease and sinus rhythm, without history of myocardial infarction). The results were indicative of possible use of ANUP as a marker of initial cardiac insufficiency and a corrector of the disease prognosis.

Isatin is an endogenous compound recently discovered in mammalian tissues and body fluids. It has a distinct distribution in rat brain, with a highest concentration, in the hippocampus, of 0.1 microgram/g. Its origin and metabolic pathways remain unclear. In vitro, isatin selectively inhibits monoamine oxidase (MAO) B (IC50 3-8 microM, Ki approximately 20 microM) and, more potently, atrial natriuretic peptide(ANP) binding (IC50, 0.4 microM). Convulsant doses of pentylene tetrazole result in increased isatin level in the brain. Small amounts of isatin are anxiogenic in rodent models, but higher doses cause sedation and possess anticonvulsant action. Isatin administration also increases monoamine levels in the brain and reduces daily urine output.

10-12-day old suckling rabbits received intragastrically culture of V. eltor 5879 and the resultant ultrastructural changes in the small intestine, atrial cardiomyocytes and capillaries were studied. In the period of cholera vibrio adhesion (4 hours after the culture administration) epithelial cells underwent hydropic degeneration. Degenerative changes due to cell vacuolization and contractile alterations were noted in cardiomyocytes of both atria. The atrial Na-uretic factor secretion prevailed over its synthesis in line with increased vascular permeability. The development of experimental cholera (on day 1-2) was characterized by balloon degeneration in the small intestinal epithelium. Numerous secretory granules were formed in the atrial cardiomyocytes without releasing peptides into the circulation. These changes are of compensatory nature and serve for liquid retention in the body. Microcirculatory disturbances take place at three levels: intravascular, endothelial and perivascular.

A recombinant plasmid providing for the synthesis and secretion of the human atrial natriuretic peptide (hANP) as a C-terminal hybrid with the St. aureus protein A was constructed. The level of secretion of the chimeric proteins and their proteolytic stability were shown to depend upon the genotype of the recipient strains and the cultivation conditions. The hybrid proteins were purified by chromatography on IgG Sepharose. The presence of peptides corresponding to the hANP in the acid hydrolysates of the secreted and affinity-purified proteins was confirmed by the enzyme-linked immunoassay and analytical HPLC.

The experiments on the rabbits and dogs have revealed that in the initial period of endotoxin shock the number of secretory granules in the atrial cardiomyocytes decreases and vascular permeability increases due to transendothelial micropinocytosis. In the intermediate period of endotoxin shock the ultrastructural alterations progress. The development of ultrastructural manifestations of endotoxemia greatly depends on the condition of endocrine heart function.

New analogues of atrial peptides of rat were synthesized by classical methods of peptide chemistry in solution. They contain a D-amino acid residue in the C-terminal part and a residue of mercaptopropionic acid in the N-terminal part of the molecule. Biological activity of the new analogues was studied.

Modern data on atrial natriuretic factor (ANF) are presented. Synthesis of this factor, its storage and release from cardiac atria are described. The role of ANF in the body fluid volume regulation and blood pressure homeostasis is discussed. ANF is regarded as a circulating hormone.

A radioimmunoassay was used to study the structural and functional status of the myocardium and blood natriuretic factor levels in 45 patients with hypertensive disease and 17 healthy subjects. Left atrial dysfunction was revealed to affect natriuretic factor levels in the blood of hypertensive patients with moderate left ventricular hypertrophy. As myocardial contractility became lower, natriuretic factor levels were reduced. The changes found in the levels in left ventricular hypertrophic variants may be accounted for by various values of intramyocardial stress. The findings suggest that cardiohemodynamic abnormalities may affect the secretion of natriuretic factor.

The results of electron microscopic studies of the synthesis and secretion of atrial natriuretic factor (ANF) in right atrial cardiomyocytes of spontaneously hypertensive rats (SHR) and the corresponding normotensive controls are presented. Enhanced secretory activity in cardiomyocytes of SHR has been revealed. The role of enhanced ANF secretion in the origin of arterial hypertension is discussed. It is suggested that enhanced ANF secretion can be attributed to increased ANF demand in BP elevation, changes in the renal function in hypertensive subjects or genetic defect in the excretory renal function in SHR.

Modern notions, accumulated during the period of investigation of before poorly studied endocrine++ function of the heart are presented. History of the problem, structural and functional aspects on argumentation of the cardiac endocrine function, place and role of physiologically active cardiac peptides in regulation of liquor and electrolytic homeostasis are followed, as well as interactions of the cardiac endocrine apparatus with the hormonal system of the organism. The authors' experience on the investigation connected with the problem is also demonstrated.