[Nitric oxide (NO) and NO cycle in myocardium: molecular, biochemical and physiological aspects].

The article continues the series of our publications on the problem of nitric oxide (NO) and its cyclic conversion in mammals. This review is held to analysis of nitric oxide role in regulation of cardiovascular system and in alocation of NO-synthases in myocardium. Molecular, biochemical and cytophysiological aspects that linked, with spatial localization of NO-synthases and mechanisms of NO content regulation in myocardium are considered. The results of author's investigations along the cyclic convertion of NO and literature data about compartmentalization of NO-synthases in myocardium are included in this paper. The contradictory and dissimilar facts about regulatory and toxic role of nitric oxide in cardiovascular system are represented.

[Nitric oxide synthase in human intracardiac ganglia in the normal and ischemic myocardium].

Nitric oxide synthase (NOS) expression in human intracardiac ganglia was studied using two techniques--histochemical demonstration of NADPH-diaphorase and immunohistochemical staining for NOS. To detect the influence of coronary heart disease on NOS expression, hearts were studied in patients that died from heart failure (n = 8) and in persons that died in accidents (n = 3, control). It was found that human intracardiac neurons normally expressed mainly NOS1, and the proportion of these cells amounted to about 40%. A portion of neurons with low and moderate density of staining for NADPH-diaphorase was increased in ischemic myocardium, probably, due NOS2 induction.

[Distribution of nitric oxide synthase in human intracardiac ganglia].

This is the first study to report presence of nitric oxide synthase (NOS) in the human intracardiac nervous cells. By applying immunohistochemical technique it was shown that majority of neuronal perikaryons contain NOS 1 (neuronal NOS). We conclude that in human heart about half of neurons have NO-ergic phenotype. These cells are also cholinergic and related to parasympathetic part of autonomic nervous system. Moreover in human heart NOS contains pericellular baskets that surround intramural neurons. This points to the presence of the enzyme in parasympathetic preganglionic fibers. A substantial differences of patterns of NOS expression in cardiac neural ganglia between humans and experimental animals are discussed.

[Significance of neuronal, endothelial and inducible NO-synthase isoforms in the cardiac muscle histophysiology].

This review summarizes the information on the interrelations between intracellular localization of NO-synthases (NOS) and their regulatory functions within different compartments of a cardiomyocyte in the light of general conception of Barouch et al. (2002) on the intracellular "spatial compartmentalization" of NOS isoforms. Participation of NO in cardiomyocyte function control is based on complex spatial compartmentalization of NOS isoforms: neuronal (NOS1), inducible (NOS2) and endothelial (NOS3), which possess unequal activities resulting in hundredfold differences in the concentrations of gas produced. Regulatory role of constititive Ca-dependent NOS1 and NOS3 is associated with production of low NO concentrations, which cause a decline in cardiomyocyte contractility and a reduction in heart rate. Conversely, Ca-independent inducible NOS2 appears only in the damaged myocardium with a compromised contractile function. NOS2 produces high unregulated NO concentrations, which are connected with the generation of peroxynitrites and NO cytotoxic action. NOS3 is associated with the membranes of cardiomyocyte caveoli and T-tubules, while NOS1 is localized on the sarcoplasmic reticulum membranes. NOS isoform compartmentalization promotes regulation of different circuits in NO-signaling pathways in myocardium, and this principle is a key for understanding of contradictions existing in NO biology in the heart. Changes in NOS subcellular compartmentalization lead to the increased NO synthesis, reduction of the specificity of its effects, disruption of calcium cycle mechanisms, electromechanical uncoupling and myocardial contractility failure. The mechanisms of selective effects of different NO-ergic regulatory pathways on the activity of five major targets in pacemaker and working cardiomyocytes, are discussed.

[Neurotransmitter stage in the development of peripheral part of autonomic nervous system]. / Mediatornyi étap v razvitii perifericheskogo otdela vegetativnoi nervnoi sistemy

The dynamics of neurotransmitter stage in the development of autonomic nervous system (ANS) was studied in rats starting from the moment of initial appearance of neurotransmitters acetylcholine and adrenalin in ANS peripheral part main nervous plexuses. Cryostat sections of embryos on developmental days 13.5, 16.5 and 18.5 and of neonatal rats aged 0.5 and 1.5 days were treated with glyoxilic acid, using Karnovsky-Roots method and impregnated with silver nitrate according to Bielschowsky-Gross method. Acetylcholinesterase in vagus and in spinal ganglia was found on day 13.5, while catecholamine in sympathetic trunc was detected in animals immediately after the birth. Periods of the beginning of neurotransmitter stage in ANS development in rat and man were compared and it was established that it was delayed in rat as in immature-born animal.