Cholinergic location of delta-opioid receptors in canine atria and SA node

Delta-opioid receptors (DORs) are associated with ischemic preconditioning and vagal transmission in the sinoatrial (SA) node and atria. Although functional studies suggested that DORs are prejunctional on parasympathetic nerve terminals, their precise location remains unconfirmed. DORs were colocalized in tissue slices and synaptosomes from the canine right atrium and SA node along with cholinergic and adrenergic markers, vesicular acetylcholine transporter (VAChT), and tyrosine hydroxylase (TH). Synapsin I immunofluorescence verified the neural character of tissue structures and isolated synaptosomes. Acetylcholine and norepinephrine measurements suggested the presence of both cholinergic and adrenergic synaptosomes. Fluorescent analysis of VAChT and TH signals indicated that >80% of the synapsin-positive synaptosomes were of cholinergic origin and <8% were adrenergic. DORs colocalized 75-85% with synapsin in tissue slices from both atria and SA node. The colocalization was equally strong (85%) for nodal synaptosomes but less so for atrial synaptosomes (57%). Colocalization between DOR and VAChT was 75-85% regardless of the source. Overlap between DOR and TH was uniformly low, ranging from 8% to 17%. Western blots with synaptosomal extracts confirmed two DOR-positive bands at molecular masses corresponding to those reported for DOR monomers and dimers. The abundance of DOR was greater in nodal synaptosomes than in atrial synaptosomes, largely attributable to a greater abundance of monomers in the SA node. The abundant nodal and atrial DORs predominantly associated with cholinergic nerve terminals support the hypothesis that prejunctional DORs regulate vagal transmission locally within the heart.     

Development and ultrastructure of the neuromuscular junction in bronchial smooth muscle tissue

At various stages of pre- and postnatal ontogenesis ultrastructure of contacts of smooth myocytes and nervous terminals in the white mice bronchial wall has been investigated. Nervous fibers grow into the forming tissue of the lung beginning from the 11th day of embryogenesis. By the end of the prenatal development the nervous fibers fasciculi with varicosites and having vesicles are localized at the distance of 100-300 nm from the developing myocytes. Formation of dense neuromuscular junctions with the distance of 35-60 nm between the axonal membranes and the myocyte is observed on the 10-15 day after birth. In mature animals combination of various types of neuromuscular connections is revealed; they ensure local and distant neurotrophic regulation. In the bronchial smooth musculature afferent connections are revealed, as well as connections of myocytic processes with the effectors. Terminals of the cholinergic type predominate, adrenergic effectors occur very seldom. There are terminals, in which combination of vesicles having various structure and diameter are observed.     

An immunocytochemical study of the sinuatrial node and atrioventricular conducting system of the rat for atrial natriuretic peptide distribution

Summary Immunocytochemical studies of the adult rat heart show that specific heart granules and atrial natriuretic peptide immunoreactivity are absent from the majority of the myocytes of the specialized nodes, atrioventricular bundle and bundle branches. Immunoreactive granules are present in a small proportion of the transitional sinuatrial and atrioventricular nodal myocytes but, in these regions, they are smaller than their counterparts in the general atrial myocytes. A rarer type of cell profile, identical to general atrial myocytes but lacking immunoreactive granules, is also present at the periphery of the sinuatrial node. A very small proportion of myocytes in the ventricular myocardium, generally in the subendocardial layers subjacent to the terminal ramifications of the bundle branches, contain a few immunoreactive granules.     

Morphologic indices of the rat heart after colchicine application to the vagus nerve

By means of the light optic and electron microscopic methods atrial ganglia, myocytes, vessels of the right cardiac chambers have been studied in rats 2 days--3 weeks after application of 100 mcg of colchicine on the right nervus vagus. Certain changes of the neural fibers have been described at the area of the application. In the myocardium the microcirculatory bed, focal edema and hypoxic alterations of the myocyte ultrastructure have been revealed. In the ventrical ganglia destruction of some terminals of the preganglionar fibers, chromatolysis and vacuolization of single neurocytes, as well as intraganglionar granule-containing cells have been found. The changes described take place for 7 days and they nearly completely disappear in 10 days. A suggestion is made that some phenomena, in particular, destruction of the preganglionar fibers and changes of the cardiac microcirculatory bed are connected with certain disturbances of the quick transport of substances in the nervus vagus fibers.     

Development of innervation to the atrial myocardium of the rabbit

Summary The development of innervation to the atrial myocardium of rabbits from 20th day of gestation to 35 days postnatal was studied ultrastructurally by electron microscopy and by demonstration of catecholamines by histofluorescence. Special attention was directed to the first morphologic appearance of nerve fibers and terminals and the closeness of juxtaposition of terminals with myocardial cells. Adrenergic and cholinergic terminals were identified on the basis of their differential ability to take-up and store the false adrenergic neurotransmitter 5-hydroxydopamine. Adrenergic terminals were first encountered at 20 days of gestation whereas cholinergic terminals could not be positively identified until the 24th day of gestation. Throughout development adrenergic terminals were more numerous than cholinergic, about 71 % of the terminals encountered being adrenergic. Many terminals approach closely (20–30 nm) to the sarcolemma of the muscle cells of the atrium. In many instances adrenergic and cholinergic fibers travel together in the same nerve bundle and are closely apposed without intervening Schwann-cell cytoplasm. Such a relationship could allow peripheral interaction between these fibers in the myocardium.Supported in part by the Kentucky Heart Association, Human Development Studies Program of the University of Kentucky and DHEW Grant 1 RO1 HL 22226-01 HED from the National Heart, Lung and Blood Institute. The technical assistance of Merle Wekstein is appreciated     

Changes in nerve terminals and acini of the lacrimal gland and changes in secretion induced by autonomic denervation

Summary Nerve terminal alterations induced by superior cervical ganglionectomy and pterygopalatine ganglion lesions, and acinus cell alterations induced by the latter operation and by greater petrosal neurectomy, established that a majority of interstitial and all parenchymal nerve terminals of the lacrimal gland in monkeys were parasympathetic. These were shown to originate from neurones of the pterygopalatine ganglion. A minority of interstitial terminals were sympathetic and were distinguished from the remainder by the presence of small granular vesicles. The number of small granular vesicles was increased by iproniazid treatment.The production of serous but not of mucous secretion granules was shown to be dependent upon a functioning parasympathetic nerve supply. Lacrimal secretion was not appreciably altered by sympathectomy but was radically reduced by parasympathectomy.Nerve terminals were closely apposed to between 15 and 56% of capillary sections. Both parasympathetic and sympathetic terminals innervated capillaries.The various experimental results are used to postulate a peripheral control mechanism for lacrimal gland secretion involving only parasympathetic nerve terminals.The author expresses his appreciation to Professor R. Warwick for the use of facilities of the Anatomy Department, Guy's Hospital Medical School.     

On the impulse conducting system of the monkey heart (Macaca mulatta)

Summary The atrio-ventricular (A-V) node of the monkey heart is located in the focus of converging atrial muscle. Three main atrial muscle strands, coming from the atrio-ventricular ring, the dorsal wall of the atria, and the ventral part of the atrial septum, converge in the nodal region where they overlap and are interconnected. The junctional type of fibers establishing interconnection between the atrial muscle and the nodal tissue are not strictly localized at the periphery of the node, but may be traced further, along the A-V ring and coronary sinus. The A-V node consists of a loose peripheral and a compact distal part. In the former, typical nodal fibers were found, while the compact part shows an important individual variation in structure and cell-types. In some monkey hearts, the nodal fibers gradually become broader bundle fibers, while in other specimens the junctional fibers surround the compact part and than penetrate the nodal-His (N-H) region. These junctional fibers become nodal fibers or are in terminal contact with large clear cells up to 50 in diameter. Clear cells of various diameters are often intercalated between the cell rows of the nodal and His-bundle fibers and may form a distinct cellular gate between the node and the His-bundle.This study was conducted in part in the Department of Histology and Embryology of the Medical University in Budapest.     

Zur Histochemie und Kapillarversorgung des Sinusknotens

Zusammenfassung Untersucht wurde der Sinusknoten von 141 Rinderherzen (davon 11 Embryonen und 50 Kälber), 25 Schweinen und 10 Herzen anderer Säuger (5 Schafe, 2 Kaninchen, 2 Katzen, 1 Hund) sowie von 29 menschlichen Herzen verschiedenen Alters.Der Sinusknoten (SK) aller Spezies ist glykogenreich; die Vorhofsmuskulatur (VM) ist vergleichsweise glykogenarm. Bei Rinderkeimlingen tritt die Glykogenvermehrung im Knotengewebe gegenüber der VM ab einer Embryonallänge von 47 cm auf.Fermenthistochemisch zeigt sich, daß im SK von Rind und Schwein nicht nur die Enzyme des oxidativen Stoffwechsels, sondern auch die der Glykolyse schwächer als in der VM reagieren. Hierbei überwiegt in beiden Herzmuskelarten die Glykolyse etwas. — Das LDH-Isozymmuster gleicht sich in SK und VM weitgehend, ebenso die Aktivität der G6P-DH und die der lysomalen Enzyme. — Die Fermente des Glykogenmetabolismus reagieren im Knotengewebe in Übereinstimmung mit seinem höheren Glykogengehalt stärker als in der VM. — Die cholinerge Nervenfaserdichte ist im SK von Rind und Schwein höher als in der VM.Entsprechend dem geringeren Stoffwechsel ist die Kapillar Versorgung des SK beim Rind geringer als die des Vorhofs. Der prozentuale Volumenanteil der Kapillaren am Gesamtvolumen des SK verhält sich zu dem der VM wie 13. Der Radius eines Gewebszylinders, der von einer Kapillare versorgt wird, beträgt im SK 19,9 m, im Vorhof aber 10,9 [im.

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On the histochemistry and capillary supply of the sinatrial node

Summary The sinatrial node (SA node) was investigated in the heart of 141 cattle (among which were 11 embryos and 50 calves), 25 pigs, 5 sheep, 2 rabbits, 2 cats, 1 dog, and 29 men of different age.The SA node of all species is rich in glycogen; in the atrial muscle its amount is always lower. Comparing the fetal SA node of cattle with the working myocardium, glycogen increases in the former tissue with an embryonic length of 47 cm.Histochemically in the SA node of cattle and pigs the activities of oxidative as well as of glycolytic enzymes are lower than in the ordinary muscle cells; but in both heart muscle systems the pathway of Embden-Meyerhof seems to predominate.—The LDH-isoenzyme patterns of the pacemaker region and working myocardium resemble one another. This is also true for the activity of G6P-DH and lysosomal enzymes.—According to the higher amount of glycogen the enzymes of the glycogen metabolism are more active in the SA node than in the atrial muscle.—In comparison with the working myocardium the number of cholinergic nerve fibers is somewhat higher in the nodal tissue.In agreement with the reduced overall metabolism the capillary supply of the cow's SA node is lower than that of the atrial muscle. The ratio between the partial volume of the capillaries and the total volumes of the SA node and working myocardium is 13. On the average the radius of a tissue cylinder being supplied by one capillary runs up to 19.9 m in the SA node, but only to 10.9 m in the atrial muscle.The partial volume of the connective tissue in the SA node of cattle, calves, and men exhibits strong individual changes. An increase of connective tissue in the SA node of humans appears around the 50th year of life.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

The ultrastructure of the atrium in the adult newt Notophthalmus viridescens (Amphibia,Salamandridae)

The atrial wall of Notophthalmus viridescens is 25–75 μm thick and is trabeculated sparsely. Coronary vessels are absent. The endocardial endothelium is continuous and has 50–60 nm-wide fenestrae with diaphragms, rests on a discontinuous basal lamina and lacks occluding junctions. Cells found in the subendothelial connective tissue are xanthophores, melanophores, mast cells, fibroblasts, macrophages, and unmyelinated nerve fibers with Schwann cell investments. Epicardial mesothelial cells contain numerous 6–7 nm filaments and lamellar bodies which resemble myelin figures. Mesothelial cell junctions include maculae adhaerentes diminutae, desmosomes, and interdigitations. The epicardial connective tissue layer is more extensive than that of the endocardium, with xanthophores and melanophores rarely present and nerve fibers never observed. The myocardium consists of a mesh-work of myocytes 3–5 cell layers thick with little intervening connective tissue. Myocytes are 6–10 μm in diameter and have two or three peripheral myofibrillae. Typical A, I, H, Z, and M bands are present with a sarcomere length of 2.5 μm. T tubules are not observed. The sarcoplasmic reticulum has subsarcolemmal dilations. The nuclear pole region contains abundant mitochondria and atrial granules, extensive Golgi, and elements of smooth and rough-surfaced endoplasmic reticulum. Lateral intercellular junctions consisting of dense plaques, frequently continuous with Z-line material, are common. Oblique and transversely oriented junctions consisting of primarily of fascia adhaerentes, are present. It appears that amphibian atrial myocytes more closely resemble those of the amphibian ventricle than those of the mammalian atrium. Structural differences between amphibian atrial and ventricular myocytes seem to be quantitative rather than qualitative in nature.     

Morpho-functional changes in the turtle midbrain tectum after enucleation

Morpho-functional changes in the tectum mesencephali during degeneration after enucleation were studied inEmys orbicularis L. Comparison of amplitude-time characteristics of evoked potentials of the visual center with degenerative changes in axon terminals and fibers of the optic nerve in the same animals revealed a "light" type of degeneration of the terminals of unmyelinated axons and a "dark" type in terminals of myelinated axons. During "dark" degeneration (4–5 months after enucleation) the low-amplitude presynaptic component of the evoked potential, reflecting excitation of large myelinated fibers, disappeared and changes occurred in the characteristics of the first high-amplitude component, the appearance of which is connected with excitation of myelinated fibers of medium diameter. The last component disappeared 7 months after the operation, along with disappearance of the "dark" degeneration. During "light" degeneration (2.5–3.5 months) changes took place in the characteristics of the second high-amplitude component of the evoked potential, which reflects excitation of thin fibers, both myelinated and unmyelinated, whose ranges of diameters overlap. This component disappeared after 6–7 months, almost simultaneously with disappearance of the first high-amplitude component, as the result of simultaneous completion of degeneration of myelinated fibers of medium and small diameter.     

Ultrastructure of the atrioventricular node of the big brown bat, Eptesicus fucus

This investigation describes the ultrastructure of the atrioventricular node of Eptesicus fuscus. Two conducting cells types (nodal and transitional) are indentified which differ in location, myofibrillar content, and types of intercellular junctions. Centrally located nodal cells display variable staining intensity and contain disorganized myofibrils which rarely form sarcomeres. Desmosomes and nexus-like junctions connect the nodal cells. Transitional cells, situated peripherally, exhibit distinct sarcomeres and are attached to the adjacent cells through desmosomes and underdeveloped intercalated discs. Longitudinal arrangement of the mitochondrial cristae is frequently seen in both cells types. In the connective tissue stroma, numerous capillaries (with micropinocytotic vesicles), axons, and possibly axonal terminals, some filled with vesicles, are observed. A large ganglionated nerve trunk is present on the nodal periphery. True nexuses and neuromuscular junctions are not observed. It is suggested that nodal cell types previously reported in different vertebrates under various names are merely simple variations of the two basic types of conducting cell--nodal and transitional. No interspecific differences are observed between these cells of the big brown bat compared with those in other vertebrates.     

Ultrastructure of the DNA-synthesizing cells of the sinoatrial node in mouse embryos according to electron microscopic autoradiographic data

By means of electron microscopic autoradiography with 3H-thymidine a study was made of the differentiation degree of DNA synthesizing muscle cells in the sinoatrial node (SAN) of the heart conductive system of the 18 day old mouse embryos. Clear myocytes (CM), predominating in the SAN at this stage, are irregular in shape, with interdigitating protrusions. Nuclei are clear, spherical or ellipsoidal. One hour following 3H-thymidine injection, about 6% of CM display labeled nuclei; this index is considerably lower than in working ventricular myocardium. Like unlabeled myocytes, CM being in phase S contain sparse, randomly located thin myofibrilles. In some areas of the sarcoplasm, only myofilament bundles and Z-disk material can be seen. The number of CM myofibrilles is always considerably less than in the working ventricular myocytes. Accumulations of intermediate (8--11 nm) filaments are present. Mitochondria with a few cristae are not numerous. The sarcoplasmic reticulum and Golgi apparatus being relatively well developed, multivesicular bodies, centrioles, and occasional cilia are often seen. Near the centrioles (basal bodies), striated filamentous bundles are found sometimes showing periodic dense lines separated by 50--70 nm. Specialized contacts between CM are rare, being presented only by desmosomes and primitive intercalated discs. Besides CM, sparse small dark cells occur filled with myofibrilles and mitochondria. In the peripheral regions of the node "transitional" cells are seen. The SAN of the 18 day old embryo mouse heart grown due to proliferation of CM with a poorly developed myofibrillar apparatus.     

Collagen and the myocardium: fibrillar structure,biosynthesis and degradation in relation to hypertrophy and its regression

The extracellular matrix of the myocardium contains an elaborate structural matrix composed mainly of fibrillar types I and III collagen. This matrix is responsible for the support and alignment of myocytes and capillaries. Because of its alignment, location, configuration and tensile strength, relative to cardiac myocytes, the collagen matrix represents a major determinant of myocardial stiffness. Cardiac fibroblasts, not myocytes, contain the mRNA for these fibrillar collagens. In the hypertrophic remodeling of the myocardium that accompanies arterial hypertension, a progressive structural and biochemical remodeling of the matrix follows enhanced collagen gene expression. The resultant significant accumulation of collagen in the interstitium and around intramyocardial coronary arteries, or interstitial and perivascular fibrosis, represents a pathologic remodeling of the myocardium that compromises this normally efficient pump. This report reviews the structural nature, biosynthesis and degradation of collagen in the normal and hypertrophied myocardium. It suggests that interstitial heart disease, or the disproportionate growth of the extracellular matrix relative to myocyte hypertrophy, is an entity that merits greater understanding, particularly the factors regulating types I and III collagen gene expression and their degradation.     

Investigating the effects of microstructural changes induced by myocardial infarction on the elastic parameters of the heart

Within this work, we investigate how physiologically observed microstructural changes induced by myocardial infarction impact the elastic parameters of the heart. We use the LMRP model for poroelastic composites (Miller and Penta in Contin Mech Thermodyn 32:1533–1557, 2020) to describe the microstructure of the myocardium and investigate microstructural changes such as loss of myocyte volume and increased matrix fibrosis as well as increased myocyte volume fraction in the areas surrounding the infarct. We also consider a 3D framework to model the myocardium microstructure with the addition of the intercalated disks, which provide the connections between adjacent myocytes. The results of our simulations agree with the physiological observations that can be made post-infarction. That is, the infarcted heart is much stiffer than the healthy heart but with reperfusion of the tissue it begins to soften. We also observe that with the increase in myocyte volume of the non-damaged myocytes the myocardium also begins to soften. With a measurable stiffness parameter the results of our model simulations could predict the range of porosity (reperfusion) that could help return the heart to the healthy stiffness. It would also be possible to predict the volume of the myocytes in the area surrounding the infarct from the overall stiffness measurements.

     

Mitotic activity of the myocardium in early ontogenesis of rabbits after minor mechanical injury to the heart

The data are provided on proliferative activity of myocytes in rabbit embryos and neonates. In rabbit embryos, in which myocardial regeneration is effected at the cellular level, mitoses of myocytes are largely important for myocyte proliferation. In rabbit neonates which do not show any complete regeneration of the myocardium, mitoses of myocytes are of primary importance for myocardial polyploidy. Minor mechanical injury to rabbit myocardium in early ontogenesis contributes to activation of the processes of hear muscle differentiation.     

Immunohistochemical localization of vasoactive intestinal polypeptide(VIP)-containing neurons in the hypothalamus of the Japanese quail,Coturnix coturnix

Summary The localization of vasoactive intestinal polypeptide (VIP) in the hypothalamus of the quail has been studied by means of light- and electron-microscopic immunohistochemistry. Numerous VIP-immunoreactive perikarya are distributed in the caudal portion of the nucleus infundibularis (n. tuberis) and nucleus mamillaris lateralis, and sparse in the preoptic area, nucleus supraopticus and nucleus paraventricularis. Dense localization of immunoreactive-VIP fibers is observed in the external layer of the median eminence, in close contact with the primary portal capillaries. The main origins of these fiber terminals are VIP-immunoreactive perikarya of the nucleus infundibularis. These neurons are spindle or bipolar and extend one process to the ventricular surface and another to the external layer of median eminence. They are CSF-contacting neurons and apparently constitute the tubero-hypophysial tract that links the third ventricle and the hypophysial portal circulation. VIP-reactive neurons in the nucleus mamillaris lateralis also project axons to the external layer of the median eminence, constituting the posterior bundle of the tuberohypophysial tract. Numerous VIP-immunoreactive perikarya occur also in the nucleus accumbens/pars posterior close to the lateral ventricle. They are also CSF-contacting neurons extending a process to the lateral ventricle. There are moderate distributions of VIP-reactive fibers in the area ventralis and in the area septalis.Ultrastructurally, the immunoreactive products against VIP are found in the elementary granules, 75–115 nm in diameter, within the nerve fibers in the median eminence.This investigation was supported by Scientific Research Grants No. 00556196, No. 56360027 and No. 56760183 from the Ministry of Education of Japan to Professor Mikami and Mr. Yamada     

Innervation of mouse lymph nodes: nerve endings on muscular vessels and reticular cells

Lymph node nerve endings have been studied in 1- to 48-day-old mice. Serial sections of Epon-embedded lymph nodes were observed under the electron microscope to find the nerve endings. Most lymph node nerve fibers finally reach the smooth muscle cells of arterioles and muscular venules. Both kinds of vascular endings are similar, although endings are less numerous on venules. Nerve endings consist of one or more nerve processes surrounded by a usually incomplete Schwann cell sheath; frequently, axons show wide areas directly facing the muscle cells. The distance between such a naked axon and a myocyte ranges from 100 to 800 nm. Small granulated and clear vesicles are especially abundant in varicosities of nerve processes that are located very close to muscle cells. Nerve endings of lymph node vasculature probably correspond to vasomotor sympathetic adrenergic endings, regulating the degree of contraction of vessels which have a muscular layer. Other kinds of nerve endings also exist in lymph nodes: some axons appear free in the stroma and contact the surfaces of reticular cells; the latter also extend delicate cytoplasmic processes that surround the axons. The functional significance of nerve cell-reticular cell contacts is unknown.     

The hypothalamo-hypophysial system of hypophysectomized rats

Summary The median eminence (ME) of hypophysectomized rats was studied by means of light and electron microscopy. Paraldehyde-fuchsin (PAF)-positive material is seen in the external zone (EZ) of the ME 2–5 days after the operation. Its amount gradually increases especially in the caudal part of the ME during the following few days. Some PAF-positive fibers make contact with the subependymally located blood capillaries. In the most caudal region of the recessus infundibuli they penetrate into the third ventricle. PAF-positive material decreases markedly from the ME of rats two months after hypophysectomy and exposure to a 1% salt load. Fibers of types A₁, A₂ and B containing granules of 120–220 nm, 100–150 nm and 80–100 nm in diameter, respectively, are seen in the EZ of the ME in hypophysectomized rats, although almost exclusively A₂- and B-type structures make contact with the primary portal capillaries in intact animals. All types of neurosecretory fibers establish contact with the subependymal nonfenestrated blood capillaries and penetrate the recessus infundibuli. Some neurosecretory terminals of different types make direct contact with the glandular cells of the pars tuberalis or are separated from them by a thin basal lamina. It is assumed that mainly neurosecretory fibers of types A₂ and B are permanently connected with the primary portal capillaries in the EZ of the ME in intact mammals, while the overwhelming majority of fibers of A₁-type shows ingrowth during the course of postoperative reparation. The possible physiological significance of the described changes is discussed.     

Cardiac enkephalins attenuate vagal bradycardia: interactions with NOS-1-cGMP systems in canine sinoatrial node

Endogenous opioids and nitric oxide (NO) are recognized modulators of cardiac function. Enkephalins and inhibitors of NO synthase (NOS) both produce similar interruptions in the vagal control of heart rate. This study was conducted to test the hypothesis that NO systems within the canine sinoatrial (SA) node facilitate local vagal transmission and that the endogenous enkephalin methionine-enkephalin-arginine-phenylalanine (MEAP) attenuates vagal bradycardia by interrupting the NOS-cGMP pathway. Microdialysis probes were inserted into the SA node, and they were perfused with nonselective (Nomega-nitro-l-arginine methyl ester) and neuronal (7-nitroindazole) NOS inhibitors. The right vagus nerve was stimulated and both inhibitors gradually attenuated the resulting vagal bradycardia. The specificity of these inhibitions was verified by an equally gradual reversal of the inhibition with an excess of the NOS substrate l-arginine. Introduction of MEAP into the nodal interstitium produced a quickly developing but quantitatively similar interruption of vagal bradycardia that was also slowly reversed by the addition of l-arginine and not by d-arginine. Additional support for convergence of opioid and NO pathways was provided when the vagolytic effects of MEAP were also reversed by the addition of the NO donor S-nitroso-N-acetyl-penicillamine, the protein kinase G activator 8-bromo-cGMP, or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. MEAP and 7-nitroindazole were individually combined with the direct acting muscarinic agonist methacholine to evaluate potential interactions with muscarinic receptors within the SA node. MEAP and 7-nitroindazole were unable to overcome the bradycardia produced by methacholine. These data suggest that NO and enkephalins moderate the vagal control of heart rate via interaction with converging systems that involve the regulation of cAMP within nodal parasympathetic nerve terminals.     

Photon radiation-induced structural and functional changes in the myocardium of hypertensive spontaneously hypertensive rats

Hypertensive SHR rates were irradiated with orange-red light using a Korobkov photon light-emitting diode matrix with a maximum radiation at 612 nm; irradiation was performed daily for 1 h for 13 days. After the course of irradiation, the rhythmoinothropic characteristics of the cardiac papillary muscle significantly improved. Morphological analysis revealed active rearrangement in myocytes, which were observed primarily in the structure of the sarcoplasmic reticulum (SR), whose relative area increased more than twice compared to the control. Apparently, photon therapy of hypertensive rats normalizes calcium homeostasis in myocytes and improves the calcium-transport function of SR. The normalization of structural and functional characteristics of the myocardium with hypertensive rates may result from an increase in the SR buffer capacity and activation of SR Ca²⁺-ATPase. Furthermore, qualitative and quantitative changes in the proportion of capillaries, myofibrils, and mitochondria in myocytes indicate the development of adaptive-compensatory processes leading to the activation of biosynthetic processes and an increase in the energy potential of the myocardium.