Effect of the adrenoreactive structures of the anterior hypothalamus on blood coagulation

In the chronic experiment stimulation of alpha- and beta-adrenoreactive structures of the anterior hypothalamus by adrenolytic substances is carried out before and after the blockade. The results of the experiments show specificity of the influence of alpha- and beta-adrenoreactive structures of the anterior hypothalamus on different phases of the process of blood coagulability.     

Mechanism of the central action of insulin on kidney function

Injection of insulin to the CSF in the presence of spontaneous diuresis and hydration gives rise to the growth of reabsorption of osmotically free water accompanied by high tubular transport, as well as to the development of antinatriuresis and inhibition of diuresis. Experiments with a preliminary blockade of beta-adrenoreceptors with propranolol or administration of a beta-blocker following insulin injection demonstrated beta-adrenoreactive brain structures to be involved in the mechanism of action of insulin. Secondary activation of vasopressin secretion and release in the blood may be mediated via these structures, as a result of which reabsorption of osmotically free water in renal tubules gets increased. Thus, CSF insulin effects its influence on renal function via the central neurohumoral mechanisms which work due to beta-adrenergic brain receptors.     

New approaches to the system regulating the aggregate state of the blood]

It is shown that in the organism there is an adrenoreactive system of the aggregate blood state regulation (ABSR) including alpha- and beta-adrenoreactive structures of hypothalamus, amygdalar complex and peripheral vessels. The ABSR system consists of two subsystems, each possessing specific action. Both subsystems interact in the reciprocal manner by the mechanism of feedbacks and can exert a modulating effect on each other.     

A mechanism for arteriolar remodeling based on maintenance of smooth muscle cell activation

Structural adaptation in arterioles is part of normal vascular physiology but is also seen in disease states such as hypertension. Smooth muscle cell (SMC) activation has been shown to be central to microvascular remodeling. We hypothesize that, in a remodeling process driven by SMC activation, stress sensitivity of the vascular wall is a key element in the process of achieving a stable vascular structure. We address whether the adaptive changes in arterioles under different conditions can arise through a common mechanism: remodeling in a stress-sensitive wall driven by a shift in SMC activation. We present a simple dynamic model and show that structural remodeling of the vessel radius by rearrangement of the wall material around a lumen of a different diameter and driven by differences in SMC activation can lead to vascular structures similar to those observed experimentally under various conditions. The change in structure simultaneously leads to uniform levels of circumferential wall stress and wall strain, despite differences in transmural pressure. A simulated vasoconstriction caused by increased SMC activation leads to inward remodeling, whereas outward remodeling follows relaxation of the vascular wall. The results are independent of the specific myogenic properties of the vessel. The simulated results are robust in the face of parameter changes and, hence, may be generalized to vessels from different vascular beds.     

The role of adrenergic structures in the control of cerebral circulation]

A study of the cerebral blood flow carried out by the thermoelectric method demonstrated that stimulation of the cervical sympathetic nerve led to marked changes in the cerebral blood supply. The blood flow changes were two-stage in character: an initial slight increase changed to a decrease below the initial level. Pharmacological analysis with the use of alpha- and beta-adrenoblockers showed a constrictor reaction of the cerebral vessels to be caused by excitation of the alpha-adrenoreactive structures, and the dilatator reaction - by the beta-adrenoreactive structures. An opinion is put forward on a possible mechanism of these changes.     

Relationship between the tonus of the walls of the internal carotid artery and cyclic adenylmonophosphate

Experiments were carried out in dogs with the use of resistography of circulatory-isolated internal carotid artery. Both activation of adenyl cyclase by adenosine and inhibition of phosphodiesterase by theophylline in the vascular wall result in a significant decrease in the vasoconstrictor effect of prestaglandin E2. On the contrary, inhibition of adenyl cyclase by the beta-blocker propranolol or activation of phosphodiesterase by imidazol in the vascular wall causes potentiation of vasoconstriction brought about by prostaglandin E2. Thus the endogenous cyclic AMP either antagonizes the vasoconstrictor effect of prostaglandin E2, or the latter affects vascular smooth muscles by influencing the activity of enzymes that are responsible for the cyclic AMP level in the vascular wall.     

Ultrastructural characteristics of elastogenesis in the major arteries of the canine hindlimb during leg lengthening

In mature dogs ultrastructural peculiarities of elastogenesis in femoral and anterior tibial arteries have been studied at various stages of the bone elongation after Ilizarov method. From the end of the 1st week of distraction, metabolic activation of intimal smooth muscle cells is revealed, from the 2d week--in the middle tunic, and on the 5th-6th week--fibroblasts of adventitia of the arteries investigated, directed to biosynthesis of intracellular predecessors of elastin and microfibrils of the elastic fibers. This results in activation of elastogenic processes, elastic structures in all three tunics of the arteries are observed to newly form and rearrange. The factor that stimulates and maintains elastogenesis is strain of extension, that occurs in the vessels during the experiment. Elastogenesis in the major arteries, when the extremity is elongated, has much in common with development of elastic components in the vascular wall in animals during the process of physiological growth.     

Effect of substrate stiffness and PDGF on the behavior of vascular smooth muscle cells: Implications for atherosclerosis

Vascular disease, such as atherosclerosis, is accompanied by changes in the mechanical properties of the vessel wall. Although altered mechanics is thought to contribute to disease progression, the molecular mechanisms whereby vessel wall stiffening could promote vascular occlusive disease remain unclear. It is well known that platelet‐derived growth factor (PDGF) is a major stimulus for the abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) and contributes critically to vascular disease. Here we used engineered substrates with tunable mechanical properties to explore the effect of tissue stiffness on PDGF signaling in VSMCs as a potential mechanism whereby vessel wall stiffening could promote vascular disease. We found that substrate stiffness significantly enhanced PDGFR activity and VSMC proliferation. After ligand binding, PDGFR followed distinct routes of activation in cells cultured on stiff versus soft substrates, as demonstrated by differences in its intensity and duration of activation, sensitivity to cholesterol extracting agent, and plasma membrane localization. Our results suggest that stiffening of the vessel wall could actively promote pathogenesis of vascular disease by enhancing PDGFR signaling to drive VSMC growth and survival. J. Cell. Physiol. 225: 115–122, 2010. © 2010 Wiley‐Liss, Inc.     

Mechanisms of blood flow-induced vascular enlargement

Chronic changes in wall shear stress lead to vascular remodeling, characterized by increased vascular wall diameter and thickness, to restore wall shear stress values to baseline. Release of nitric oxide from endothelial cells exposed to excessive shear is a fundamental step in the remodeling process, and potentially triggers a cascade of events, including growth factor induction and matrix metalloproteinase activation, that together contribute to restructuralization of the vessel wall. Understanding these processes could help explain how changes in blood vessel wall structure occur in the context of atherosclerosis or aortic aneurisms.     

云南野生稻叶茎根组织结构特性的比较研究

采用徒手切片法对云南3种野生稻和栽培稻的叶片、茎秆及根的组织结构进行比较研究,以明确野生稻的内部结构,为进一步揭示其结构与云南野生稻的生长势旺盛、营养吸收能力强、抗某些病虫害能力强的关系奠定基础。结果表明,(1)云南野生稻与栽培稻叶片主脉、茎秆及根的组织结构差异显著,其中景洪疣粒野生稻、景洪药用野生稻与栽培稻的差异最明显。(2)在叶主脉结构中,景洪疣粒野生稻无气腔结构,维管束数量少、面积小;景洪药用野生稻、3个普通野生稻材料存在多个维管束和气腔结构,维管束、束内导管直径及气腔面积较栽培稻大,而栽培稻中的气腔均为2个。(3)在茎秆结构方面,景洪疣粒野生稻茎秆最小,维管束数量最少,其茎壁内的维管束排列方式与栽培稻不同;景洪药用野生稻和普通野生稻茎秆及茎壁较栽培稻粗厚,维管束数量也较栽培稻多,普通野生稻的茎壁中有通气组织。(4)在根的组织结构中,3种野生稻的导管数量较多,导管直径及中柱面积较栽培稻大,外皮层出现了具有凯氏带功能的凯氏点等。     

The effect of lipoproteins on signal transduction in thrombocytes and vascular wall cells

In recent decades, studies have shown that lipoproteid physiological role goes beyond just their part in lipid transport. Database is accumulating on connection of lipoproteid pathological effects upon cardiovascular system with their ability to interfere in the signal transmission processes necessary for normal control of the vascular homeostasis. There is some evidence that lipoproteids are capable of affecting vascular tonus, coagulation balance, and inflammatory processes in the vascular wall. These effects will be realized through activation of the blood cell and vascular wall signal systems and can accelerate development of atherosclerosis and prompt hypertension and arterial thrombophilia.     

Ultrastructure of the pulmonary trunk wall during the prenatal period of ontogenesis

By means of transmissive electron microscopy stages of morphogenesis have been studied in the pulmonary trunk wall of 12 healthy human embryos and fetuses of 5-24-week-old. There is a close dependence in development of the smooth muscle component of the middle tunic, elastic and collagenous fibers of the pulmonary trunk wall. In the early prenatal morphogenesis of the pulmonary trunk fibrillogenesis develops intensively, overtakes the differentiation time of myocytes from mesenchymal cells, the collagenous fibers appearing earlier than the elastic ones. The structures, that ensure solidity of the vascular wall (collagenous fibers), appear in embryogenesis earlier that those, ensuring its elasticity (ability to reversible deformity).     

Protein Kinase N1 Is a Novel Substrate of NFATc1-mediated Cyclin D1-CDK6 Activity and Modulates Vascular Smooth Muscle Cell Division and Migration Leading to Inward Blood Vessel Wall Remodeling

Toward understanding the mechanisms of vascular wall remodeling, here we have studied the role of NFATc1 in MCP-1-induced human aortic smooth muscle cell (HASMC) growth and migration and injury-induced rat aortic wall remodeling. We have identified PKN1 as a novel downstream target of NFATc1-cyclin D1/CDK6 activity in mediating vascular wall remodeling following injury. MCP-1, a potent chemoattractant protein, besides enhancing HASMC motility, also induced its growth, and these effects require NFATc1-dependent cyclin D1 expression and CDK4/6 activity. In addition, MCP-1 induced PKN1 activation in a sustained and NFATc1-cyclin D1/CDK6-dependent manner. Furthermore, PKN1 activation is required for MCP-1-induced HASMC growth and migration. Balloon injury induced PKN1 activation in NFAT-dependent manner and pharmacological or dominant negative mutant-mediated blockade of PKN1 function or siRNA-mediated down-regulation of its levels substantially suppressed balloon injury-induced smooth muscle cell migration and proliferation resulting in reduced neointima formation. These novel findings suggest that PKN1 plays a critical role in vascular wall remodeling, and therefore, it could be a promising new target for the next generation of drugs for vascular diseases, particularly restenosis following angioplasty, stent implantation, or vein grafting.     

Regulation of smooth muscles of the vascular wall in the rabbit pulmonary artery

The cholinergic, histaminergic and adrenergic features of regulation of the small muscles contractile activity in a vascular wall of a pulmonary artery in rabbits and involvement of an endothelium in these processes, were investigated. The cholinergic release phenomenon of small muscles of the rabbit pulmonary artery has a two-component character of dose dependence. The low-threshold components of Pilocarpinum relaxing effect has an endothelium-dependent nature. The important feature of histaminergic regulation of contractile activity of segments involves a direct contractile effect of histamine that is not inherent. The endothelium renders a suppressing effect on histaminergic contraction of small muscles of the rabbit pulmonary artery. A basic feature of adrenergic regulation of the pulmonary artery involves registered-beta-adrenergic contractile effects in small muscles of a vascular wall. The activation of the cAMP-dependent signal system in small muscles of a pulmonary artery is capable of rendering a contractile effect. The detected features of a regulation in the small circle can have an essential clinical-physiological value.     

Lymphocyte recirculation and homing: roles of adhesion molecules and chemoattractants

Lymphocyte migration from high endothelial venules into lymphoid organs is mediated by a sequence of interactions between cell adhesion molecules on lymphocytes and those on the vascular endothelial cells that line the vessels. recent studies suggest that the so-called lymphocyte homing receptors and vascular addressins regulate the first stages of this process, that of binding of lymphocytes from flowing blood. The subsequent crawling of lymphocytes over the endothelial cell surface and migration across the vessel wall (diapedesis) are regulated independently of initial binding. These latter stages are thought to be mediated by functional activation of integrins on the lymphocyte by chemoattractants located in the vessel wall.     

Vascular alterations upon activation of TGFβ signaling in fibroblasts - implications for systemic sclerosis

Tissue fibrosis and vascular disease are hallmarks of systemic sclerosis (SSc). Transforming growth factor β (TGFβ) is a key-player in fibroblast activation and tissue fibrosis in SSc. In contrast to fibrosis, evidence for a role of TGFβ in vascular disease of SSc is scarce. Using a transgenic mouse model with fibroblast-specific expression of a kinase-deficient TGFβ receptor type II, Derrett-Smith and colleagues demonstrate that aberrant TGFβ signaling in fibroblasts might result in activation of vascular smooth muscle cells and architectural changes of the vessel wall of the aorta.     

Control of blood vessel structure: insights from theoretical models

Blood vessels are capable of continuous structural adaptation in response to changing local conditions and functional requirements. Theoretical modeling approaches have stimulated the development of new concepts in this area and have allowed investigation of the complex relations between adaptive responses to multiple stimuli and resulting functional properties of vascular networks. Early analyses based on a minimum-work principle predicted uniform wall shear stress in all segments of vascular networks and led to the concept that vessel diameter is controlled by a feedback system based on responses to wall shear stress. Vascular reactions to changes in transmural pressure suggested feedback control of circumferential wall stress. However, theoretical simulations of network adaptation showed that these two mechanisms cannot, by themselves, lead to stable and realistic network structures. Models combining reactions to fluid shear stress, circumferential stress, and metabolic status of tissue, with propagation of stimuli upstream and downstream along vascular segments, are needed to explain stable and functionally adequate adaptation of vascular structure. Such models provide a basis for predicting the response of vascular segments exposed to altered conditions, as, for example, in vascular grafts.     

Local blood flow in the emotiogenic structures of the brain in freely moving rats

The speed of local blood flow (SLBF) in positive emotiogenic hypothalamic zones was recorded in free-moving white rats, by the method of hydrogen clearance, in states of passive and active alertness, in conditions of artificial (local) activation (by cathode) and inactivation (by DC anode) and also during stimulation of other positive and negative emotiogenic structures. It was established that the natural or artificial activation of the emotiogenic brain zones elicits an increase of SLBF and the inactivation evokes its reduction. Blood flow of the positive emotiogenic brain zones is intensified by stimulation of other positive emotiogenic structures, is reduced by stimulation of the negative emotiogenic zones and does not change at stimulation of emotionally neutral zones. It is suggested, that the mechanism of vascular reactions elicited by activation of positive and negative emotiogenic brain structures has a neurogenic basis and is performed in the type of "axon-reflex" by collaterals of ascending and descending fibers of the forebrain medial bundle.     

A possible role of the oxidant tissue injury in the development of hypoxic pulmonary hypertension

Chronic sojourn in hypoxic environment results in the structural remodeling of peripheral pulmonary arteries and pulmonary hypertension. We hypothesize that the pathogenesis of changes in pulmonary vascular structure is related to the increase of radical production induced by lung tissue hypoxia. Hypoxia primes alveolar macrophages to produce more hydrogen peroxide. Furthermore, the increased release of oxygen radicals by other hypoxic lung cells cannot be excluded. Several recent reports demonstrate the oxidant damage of lungs exposed to chronic hypoxia. The production of nitric oxide is high in animals with hypoxic pulmonary hypertension and the serum concentration of nitrotyrosine (radical product of nitric oxide and superoxide interaction) is also increased in chronically hypoxic rats. Antioxidants were shown to be effective in the prevention of hypoxia induced pulmonary hypertension. We suppose that the mechanism by which the radicals stimulate of the vascular remodeling is due to their effect on the metabolism of vascular wall matrix proteins. Non-enzymatic protein alterations and/or activation of collagenolytic matrix metalloproteinases may also participate. The presence of low-molecular weight cleavage products of matrix proteins stimulates the mesenchymal proliferation in the wall of distal pulmonary arteries. Thickened and less compliant peripheral pulmonary vasculature is then more resistant to the blood flow and the hypoxic pulmonary hypertension is developed.     

Extrinsic and intrinsic cholinergic systems of the vascular wall.

Immunohistochemical, biochemical and functional studies have revealed two separate cholinergic systems in the arterial vascular wall. Endothelial cells represent the ubiquitous intrinsic, intimal system; they contain the acetylcholine-synthesizing enzyme, choline acetyltransferase, release a choline ester, and contain functional muscarinic receptors. Perivascular autonomic nerve fibres represent the extrinsic, adventitial system. These axons are not ubiquitous but show a highly selective distribution among and even within organs, and utilize co-mediators (NO, neuropeptides) in an organ-specific pattern. We put forward the hypothesis that the intrinsic, intimal system serves as a general regulator of basal vascular tone and wall structure responding to local, luminal stimuli, whereas the perivascular nerve fibres act on top of this basal tone by providing fine tuning in response to reflex activation due to systemic demands.