摘要:

ABSTRACTThe microcirculation of the synovial lining of joints displays many fascinating adaptations to function. One primary function is to supply nutrients to the avascular cartilage, whose chondrocytes are metabolically active but are relatively vast distances from the nearest capillary (>1 cm in the center of a human knee). Exchange is facilitated by a high density of fenestrated capillaries situated very close to the synovial surface (an arrangement disrupted in rheumatoid synovium) with fenestrations preferentially oriented toward the joint cavity. Even so, diffusion alone is too slow to supply central chondrocytes with glucose. The problem is solved by the synovial microcirculation generating intra‐articular fluid (synovial fluid) that transports glucose by convection during joint movement. Synovial fluid is a plasma ultrafiltrate into which hyaluronan has been secreted, and it also serves to lubricate the joint.The joint cavity offers unusually easy access to the interstitial side of the microcirculation because the synovial cell layer is discontinuous, with an interstitial matrix between capillary and joint cavity. This allows the experimental study of the effect of the extravascular Starling “forces” (hydraulic and colloid osmotic pressure) on fluid exchange. One unexpected outcome has been the finding that a substantial part of the hydraulic resistance to fluid transport between blood and joint cavity resides in the series interstitial layer rather than in the capillary wall. Another is that, under appropriate boundary conditions (joint angle, etc.) fluid can simultaneously filter into the cavity in some regions (synovium directly overlying capillaries) and out of the cavity into subsynovium in other regions (synovium in the mesh space between capillaries) to produce a turnover of synovial

ISSN:1073-9688    

DOI:10.3109/10739689509146768

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

ABSTRACTThere is a growing body of evidence that nitric oxide modulates the movement of fluid and protein out of the vasculature. However, the results obtained from whole organ, single vessel, and endothelial monolayer studies are often not consistent. In fact, there is much evidence that endogenous nitric oxide increases microvascular permeability and equally compelling evidence to suggest that endogenous nitric oxide decreases microvascular permeability. In this review we summarize and critically evaluate the data published to date regarding the role of nitric oxide as a modulator of microvascular permeability under both normal conditions and following exposure to various stimuli. The last section of the chapter discusses the importance of nitric oxide as a modulator of microvascular permeability in inflammatory conditions. Particular emphasis is placed on the stimuli used, the organ systems studied, and the measurements performed to investigate the effects of nitric oxide on microvascular permeability alterations.

ISSN:1073-9688    

DOI:10.3109/10739689509146769

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

ABSTRACTThe present overview is intended to serve several purposes. It highlights efforts over the years to resolve the difficult key issues raised by August Krogh in the 1930s and by the urgent need created in the 1940s and 1950s by World War II to come to grips with the basic problems underlying the collapse of tissue perfusion in the syndrome of circulatory shock. The complex operational issues raised by circulatory insufficiency at the systemic, as well as the local tissue level, during the shock syndrome, are used as a framework to keep in perspective the impact of advances in methodology, ultrastructure, and in recent years in molecular biology on microvascular research. In view of the current continuing need to integrate the newly emerging body ofin vitroinformation into specific aspects of the operation of the peripheral vascular tree, emphasis is placed on the advances in dealing with data provided byin vivomicroscopy of selected tissues.This overall review has made it clear that a top priority remains the need to separate the effects of systemic and locally derived readjustments, and to identify the basis for the substantial differences in cellular behavior exhibited by the vascular and perivascular components of the various organs and tissues of the body that can serve as predisposing factors in regional pathophysiology.

ISSN:1073-9688    

DOI:10.3109/10739689509146770

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

ABSTRACTObjective:To determine which interstitial collagen types may be present in bovine retinal microvessel extracellular matrix (ECM).Methods:Dissociated bovine microvessels were treated with detergents and the resultant purified ECM monitored by transmission electron microscopy (TEM). Pepsin‐extracted soluble ECM collagens were identified by Western blots. Collagens were further purified by neutral salt precipitation and carboxymethyl cellulose (CMC) chromatography before cyanogen bromide (CNBr) peptide mapping and two‐dimensional peptide mapping of CMC‐generated fractions. Interstitial collagens were localized by immunofluorescence on frozen sections.Results:Transmission electron microscopy of detergent‐purified microvessel ECM demonstrated numerous 10–50‐nm collagen fibrils associated with basal laminae regardless of vessel diameter. Western blots showed that soluble ECM collagens were strongly positive for type II, moderate for type III, and weak for type I. CNBr peptide maps and two‐dimensional maps of neutral salt and CMC‐purified fractions confirmed the presence of type II collagen. Immunofluorescence localized type II collagen in large and small vessels of the retina.Conclusions:Type II collagen is an unexpected major component of bovine microvessel ECM, whereas types I and III are present in minor amounts. Type V collagen is also a substantial ECM component. Accordingly, all four types may contribute to a heterogeneous population of collagenous fibrils identified by TEM in intact isolated retinal

ISSN:1073-9688    

DOI:10.3109/10739689509146771

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

ABSTRACTObjective:The cellular basis for spatial heterogeneity along postcapillary venules in their response to inflammatory mediators is not understood. To study permeability regulatory processes on an individual cell basis in intact microvessels, we developed methods to delineate individual endothelial cells within living, single perfused microvessels.Methods:Individual postcapillary microvessels in the mesenteries of frogs and hamsters were perfused with chloride‐free Ringer's solutions containing AgNO3(0.1 g per 100 ml) for 5–10 s. Vessels were immediately flushed with Ringer's solution containing serum albumin and some vessels subsequently perfused with the fluorescent nucleic acid stain YO‐PR0‐1 (1 μM) for 10–15 min. Vessels were imaged in situ using laser scanning confocal microscopy. A reflectance image from silver precipitate in the endothelial clefts and a fluorescence image of the nuclei were simultaneously recorded. Stacks of confocal images were merged and used to reconstruct the three‐dimensional orientation of endothelial cells. Hydraulic conductivity of some frog mesenteric venular vessels, measured before and after perfusion with AgNO3, was used to assess the integrity of the vessels.Results:The endothelial cell clefts were delineated with a very fine, readily imaged precipitate of silver. Hydraulic conductivity measured after AgNO3perfusion in frog mesenteric venular microvessels was not significantly different from control. Vessels showed a slight reduction in reactivity to inflammatory stimuli. The three‐dimensional pattern of endothelial cells in the living vessels was imaged.Conclusions:Combining confocal microscopy with silver staining in single perfused microvessels was shown to be an effective means to delineate the three‐dimensional pattern of endothelial cells forming microvessel walls. It enables further study of the vascular structure and function relationships at the individual cell level in int

ISSN:1073-9688    

DOI:10.3109/10739689509146772

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

ABSTRACTObjective:Provide regional flow measurement in the hearts of small mammals using a new, higher‐resolution technique based on the deposition of a molecular marker.Methods:We determined the instantaneous extraction and retention of the “molecular microsphere” radiolabeled desmethylimipramine in retrogradely perfused hamster hearts. In a separate series of experiments, autoradiography was used to measure regional myocardial deposition densities in hamster hearts of about 0.5 g with spatial area resolution of 16 × 16 μm.Results:Radiolabeled desmethylimipramine is almost 100% extracted during a single transcapillary passage and is retained in the tissue for many minutes. Autoradiographic images demonstrated a spatial flow heterogeneity with standard deviations of 31 ± 4% of the mean flow (N= 5) in 16 × 16 × 20‐μm3voxels. This is equivalent to the projections made using fractal relationships from cruder observations obtained with microspheres in the hearts of baboons, sheep, and rabbits.Conclusion:Autoradiography using a molecular deposition marker provides quantitative information on myocardial flow heterogeneities with resolution at the size of cardiac myocytes. Because the regions resolved are smaller than the volume of regions supplied by single arterioles, the results must slightly exaggerate the true heterogeneity of r

ISSN:1073-9688    

DOI:10.3109/10739689509146773

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

ABSTRACTObjective:To determine whether putrescine, a naturally occuring polyamine, is able to prevent nonenzymatic glycosylation‐induced cross‐linking of basement membrane components. Cross‐linking, leading to the formation of advanced glycosylation end products (AGEs) has been proposed as a major mechanism contributing to structural and functional changes of the vascular wall, thus leading to microangiopathy.Methods:Laminin, a major basement membrane glycoprotein present in the microvasculature, was isolated and incubated in the presence of high glucose concentrations, in order to generate an in vitro diabetic environment. Putrescine was either present or absent from the incubation mixture. Formation of cross‐links was assessed by two independent methods: gel electrophoresis and development of characteristic fluorescence.Results:Putrescine inhibited in a dose‐dependent manner the formation of slower mobility bands in gel electrophoresis. Quantitation of the development of fluorescence characteristic of glycosylation‐induced cross‐links demonstrated that putrescine inhibited the formation of fluorescent products.Conclusions:Putrescine may be a promising compound for inhibition of protein cross‐linking and, therefore, could be used in the prevention of diabetic

ISSN:1073-9688    

DOI:10.3109/10739689509146774

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

ABSTRACTObjective:To test the hypothesis that the diameter of skeletal muscle arterioles is determined by the interaction of responses elicited by intravascular pressure and flow.Methods:Experiments were conducted on isolated, cannulated, first‐order arterioles of cremaster muscle of male Wistar rats. The diameter of arterioles was followed by videomicroscopy. Perfusion pressures and flows were controlled.Results:In the absence of perfusate flow, increases in perfusion pressure (from 0 to 120 mm Hg), after initial dilation, elicited endothelium independent constrictions of arterioles. At 60 mm Hg of perfusion pressure, the active diameter of vessels was 84.9 ± 1.9 μm. The passive diameter of arterioles (Ca2+‐free solution) was 150.6 ± 2.4 μm. Increases in perfusate flow resulted in a significant upward shift in the pressure—diameter curves; in the presence of perfusate flows of 20, 40, and 60 μL/min, the constriction of the vessels at a pressure of 60 mm Hg was attenuated by 25.1 ± 3.9%, 35.2 ± 3.0%, and 46.8 ± 4.4%, respectively. In contrast, the corresponding diameter of arterioles at perfusate flows of 10 to 60 μL/min was significantly reduced when perfusion pressure was increased from 60 to 80 and 100 mm Hg (at a flow of 60 μL/min) by 12.0 ± 4.3% and 37.1 ± 2.8%, respectively. Hence, both flow‐ and shear stress—diameter curves were significantly shifted downward when perfusion pressure increased from 60 to 100 mm Hg.Conclusion:These results demonstrate that an interplay between pressure and flow‐sensitive mechanisms is an important determinant of the arteriolar resist

ISSN:1073-9688    

DOI:10.3109/10739689509146775

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:1073-9688    

DOI:10.3109/10739689509146776

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:1073-9688    

DOI:10.3109/10739689509146777

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY