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Biomedical subjects

E Betz

Publications and source records attributed to E Betz.

At least 55 records · Page 3Linked to original sources
PubMed1988

The effect of pentoxifylline on endothelial permeability of rabbit carotid artery wall.

Weak electrical stimulation of the rabbit carotid artery wall with direct current impulses over a period of 45 min increased the endothelial permeability for horseradish peroxidase (HRP), molecular weight 40,000 Da, beneath the anode region of the electrodes. The stimuli caused a massive accumulation of the reaction products of peroxidase in the subendothelial space. With a microdensitometric technique, it was possible to quantify the amount of the peroxidase reaction products in the subendothelium, and to compare the amounts in the non-stimulated regions with those in the stimulated regions. Intravenous administration of pentoxifylline before stimulation inhibited the transendothelial transport of peroxidase. Inhibition was pronounced in the stimulated regions, whereas the uptake of HRP in the non-stimulated regions was only slightly lower than that in non-treated animals. It was demonstrated that the extent of inhibition was dose-dependent (3, 10 and 30 mg pentoxifylline/kg). Electron microscopic examination showed that the main route of permeation of HRP was through the interendothelial clefts. However, electrical stimulation also caused an increase in the vesicular uptake of HRP into endothelial cells. Both pathways seem to be influenced by pentoxifylline.

Animals↗
PubMed1988

Expression of smooth muscle myosin in relation to growth kinetics of cultured aortic smooth muscle cells.

The goal of this study is to quantify smooth muscle myosin (SMM) expression at the level of the individual cell and to ascertain whether SMM expression in cultured aortic smooth muscle cells is related to definite growth phases, and whether the initial seeding density affects growth or SMM staining. Rabbit aortic smooth muscle cells (SMCs) were harvested by enzyme digestion of aortic tissue and plated at low (100 cells cm-2), medium (1000 cells cm-2), and high (10,000 cells cm-2) densities. Independent of seeding density, the lag phase lasted 2 to 3 days and, at all three densities, the growth rate during the logarithmic growth phase was almost the same. However, the time, the number of population doubling needed to reach the plateau phase and the cell number in the plateau were influenced by the initial seeding density. Immunofluorescence staining with anti-smooth muscle myosin (ASMM) revealed intensive staining of striated and filamentous patterns in all cells during the lag and early logarithmic growth phases. During the late logarithmic growth phase, two subpopulations of cells appeared, one showing a positive and the other no reaction with SMM antiserum. The lowest relative number of cells which showed positive reactions with SMM antiserum was observed toward the end of the logarithmic growth phase. During the plateau phase, the SMM-positive subpopulation increased, amounting to about 60% of the total number of cells, independent of the seeding density. In terms of absolute numbers, the number of SMM-positive cells increased over the course of 21 days by factors of 13, 72, and 342 for high, medium, and low seeded cultures, respectively. We conclude that a SMC subpopulation can divide without loss of SMM and that some, but not all, cells which lose their SMM may possibly regain it in the postconfluent state.

Animals↗
PubMed1987

Temporal sequence of morphological alterations in artery walls during experimental atherogenesis--occurrence of leukocytes.

In rabbit carotid arteries arteriosclerotic lesions were induced by repeated local transmural electrical stimulations. The sequence of early morphological alterations in the vessel wall and especially the kinetics of leukocytes were examined by transmission electron microscopy. After a stimulation period of only 1 day monocytes and heterophilic granulocytes adhered to the endothelial surface. In the subendothelium mainly beneath the anode, focal amorphous insudates were present together with mononuclear and granulocytic cells. Thereby, the endothelium was maintained as a continuous lining as shown by surface staining with silver nitrate. However, both pattern and size of the endothelial cells were altered in comparison to the controls. Some of the endothelial cells displayed a heavy cytoplasmic silver salt deposition. After 2 days of the electrical stimulation schedule, the first myocytes occurred in the subendothelial space. The mediamyocytes sending pseudopods through the internal elastic lamina still appeared to be in a contractile phenotype. In the 7-day-old proliferative lesion modulated smooth muscle cells were the predominant cell type; only 10%-20% of the subendothelial cells were identified as macrophages and heterophils. This proportion decreased further, and after a stimulation period of 28 days the granulocytes disappeared completely. At this stage of plaque development, the intimal myocyte population mainly consisted of contractile smooth muscle cells and intermediary states between the contractile and modulated phenotype. The insudation, immigration of white blood cells, and subsequent migration and proliferation of myocytes reinforces the view that the initial phases of arteriosclerotic lesions may represent a special form of an inflammatory response.

Animals↗
PubMed1987

Cytocontractile structures and proteins of smooth muscle cells during the formation of experimental lesions.

The time course of structural changes in vascular smooth muscle cells (SMC) was investigated during the formation of an experimental lesion in response to balloon injury. We compared the filamentous organization, evaluated by quantitative electron microscopy, with the cellular content of two representative cytocontractile proteins (myosin and tropomyosin) as assessed by immunofluorescence. We found that the changes peak between 7 and 14 days after injury and that they are visible both in the neointima and to a lesser extent in the inner media. While virtually all SMC are of a filament-rich phenotype in the undisturbed media, after balloon injury SMC migrated into the intima and about 90% of these latter cells were either of a organelle-rich or an intermediate phenotype, with the remaining 10% being of the filament-rich phenotype. In the inner media about 40% of cells were either of organelle-rich or intermediate phenotype. In contrast to these profound organizational changes of responding SMC, histochemistry revealed only a slight and probably transient decrease of the cellular content of myosin and tropomyosin at that time point. Twenty-eight days after injury the discrepancies between the content and the organization of cytocontractile proteins became more apparent. While virtually all SMC showed a homogeneous intensive staining with both antibodies, indistinguishable from the media SMC, the organization of cytoplasmic filaments had not totally recovered. Even though this morphological study does not permit conclusions to be drawn on the contractile function of the cells, it shows that both the organization and the content of cytocontractile protein have to be analyzed and compared for SMC changes to be evaluated during the formation of an experimental lesion.

Angioplasty, Balloon↗
PubMed1987

[The pathophysiology of cerebral circulation].

Local and generalized decreases in cerebral circulation most frequently cause severe functional and morphological disturbances in the central nervous system. During a generalized cerebral ischemia, the appearance of signs of disturbances in electrical and metabolic functions follows a characteristic course. These changes have been demonstrated in experimental examples. In severe hypoxia with occlusion of cerebral arteries, the changes in energy metabolism and electrical phenomena are similar to those in ischemia. The typical signs of oligemic hypoxia, anoxic and hypoxic hypoxia, anemic hypoxia, venous hypoxia and histotoxic hypoxia are characterized in this review. In energy deficient brain tissue the ionic fluxes across the membranes of nerve cells, as well as across the smooth muscle cell membranes of the cerebral artery walls, are of particular interest. Cations have been investigated frequently and in this report the interactions between ions which participate in the regulation of vessel wall tension are discussed. Finally, the redistribution of blood flow after occlusion of single brain-supplying arteries is described.

Brain↗
PubMed1986

Orientation of cultured arterial smooth muscle cells growing on cyclically stretched substrates.

Arterial smooth muscle cells from rabbit aortic media were grown in first subcultures on hydrophilized and collagen-coated silicone membranes which were then subjected to directional cyclic stretches and relaxations at a frequency of 50 times/min. The membranes were stretched 2, 5 and 10% beyond their resting length. Cells on unstretched and stationary membranes in the same chamber served as controls. The cells which were stretched with an amplitude of 2% remained in random orientation after 14 days of continuously performed cyclic stretching. The cells which were stretched 5% for 12 days orientated at an angle of 61 +/- 9 degrees to the direction of stretching, while the cells which were stretched with an amplitude of 10% for 6 days orientated at an angle of 76 +/- 5 degrees. The cells on the stationary and unstretched membranes remained in random orientation. We were able to confirm that the angle of orientation is reversible, i.e. preorientated cells changed their orientation during application of another stretching amplitude. The results suggest that stretching of the artery wall by blood pulsation may be a factor influencing the orientation of smooth muscle cells within the media of the artery wall and of those smooth muscle cells which proliferate into the subendothelial space after mechanical injury of the endothelium or electrical stimulation of the artery wall. An apparatus is presented which produces cyclic and directional mechanical stimuli similar to those which may occur in the artery wall.

Animals↗
PubMed1986

Co-cultivation of endothelial and smooth muscle cells on opposite sides of a porous membrane.

A co-culture system is here proposed that mimics the topographical situation of the vessel wall in which endothelial cells are separated by a fenestrated elastic lamina from smooth muscle cells. Bovine aortic endothelial cells were grown on one side of a thin microporous membrane and smooth muscle cells were cultivated on the other side. The microporous membrane was inserted in a special frame so that a two-compartment system was created. The membrane may act like the fenestrated internal elastic lamina of arteries in allowing interactions and fluid exchanges between the two cell types through its pores. Membranes were examined both by transmission and scanning electron microscopy to evaluate the morphology of both cell types.

Animals↗
PubMed1986

The role of calcium in the regulation and dysregulation of cerebral blood flow.

Calcium influences the cerebral artery system not only through its action on the contractile state of the vessels' SMC, but also acts in the regulation of transendothelial transports of macromolecules. Additionally it plays a decisive role in migration and proliferation of SMC during the formation of atheromas. By means of calcium entry blockers used in vivo and in cultures of SMC and fibroblasts the significance of calcium for pathophysiological reactions of the cerebrovascular system is elucidated.

Animals↗
PubMed1986

Effect of etofibrate and its metabolites on atheromas of rabbits and on smooth muscle cell cultures.

In rabbits electrodes were implanted on either side of a carotid artery wall in a way such that transmural electrical stimulation could be performed on the unrestrained animal. Daily repetition of stimulation (100 microA, 10 Hz, 10 ms/imp), 30 min in the morning and 15 min in the afternoon, causes a fibromuscular intimal proliferate below the anode. With additional feeding of a cholesterol-rich diet the proliferate develops into a typical atheroma. The use of defined intensity of the stimuli and a constant period of stimulation (4 weeks) allows a standardization of the plaque development and thus the study of the effects of growth promoting or growth suppressing drugs. The in vivo experiments were supplemented with a study of the effects of the same drugs on the growth of vascular smooth muscle cells and fibroblasts in cell cultures. This combination of experiments increased the value of either results given that the drugs show similar effects in both types of experiments. 2-[2-(p-Chlorophenoxy)-2-methylpropionoxy]ethyl nicotinate (etofibrate, Lipo-Merz) was seen to inhibit the growth of atheromas to a certain degree in vivo. A dose dependent suppression of the rate of mitoses of vascular smooth muscle cells (SMC) and of fibroblasts was observed in vitro. Etofibrate caused a slight decrease in the serum cholesterol and a significant increase in serum high density lipoproteins in the animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Inhibition of smooth muscle cell proliferation and endothelial permeability with flunarizine in vitro and in experimental atheromas.

Repeated weak electrical stimulations of rabbit carotid artery walls with implanted electrodes cause intimal proliferations of smooth muscle cells (SMC) and lead to fibromuscular plaques beneath the anode. If the animals receive a cholesterol-enriched diet the plaques become typical atheromas. The endothelial lining is maintained. The procedure for the production of an atheroma with 11 +/- 4 layers of SMC lasts 4 weeks. Addition of the calcium antagonist Flunarizine to the food during the stimulation periods inhibits the growth of the plaque. The inhibition is dose-dependent. Whether the drug inhibits atherogenesis by direct action on SMC or via an effect on permeation of macromolecules through the endothelium has been studied by measurement of (1) peroxidase (MW 40,000 dalton) permeability through the stimulated endothelium of the artery and (2) the inhibitory effects of Flunarizine on cultures of arterial SMC. Endothelial permeability increases for some hours after stimulation mainly beneath the anode. Flunarizine inhibits the permeation of peroxidase through the endothelial lining for the most part by its action on intercellular transport. The drug also inhibits the growth of SMC in mass cultures and clone cultures. The inhibition of proliferation is not specific for SMC. Skin fibroblasts obtained from the same animals as the artery smooth muscle cells are also inhibited in mass cultures and clone cultures. From the results it can be concluded that Flunarizine exerts its inhibitory action not only by its effect on the permeation through the endothelial lining but by a combined action on permeability and proliferation of cells in the artery wall.

Animals↗
PubMed1983

[Effect of benzarone on the oxygen consumption and the mechanical activity of vascular smooth muscle].

The influence of 2-ethyl-3-(4-hydroxy-benzoyl)-benzofurane (benzarone, Fragivic) on the energy metabolism of the wall of the rabbit common carotid artery and the rat portal vein was investigated by measuring the oxygen consumption of in vitro incubated vessel segments. Benzarone increased the oxygen consumption of the carotid artery either in whole vessel wall segments or in intima-media preparations. The increase was concentration-dependent. The basal tone of the artery did not change during incubation. Benzarone decreased the oxygen consumption of the portal vein, while spontaneous phasic activity was blocked and the basal tone lowered. The results suggest that, besides its antagonistic effects on mediators of muscle contraction, benzarone influences the metabolism of the smooth muscle cells directly. An uncoupling effect on the oxidative phosphorylation, which would be consistent with the antiinflammatory properties of benzarone, is discussed.

Animals↗