ISSN:1062-3329    

DOI:10.3109/10623329309102313

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Until recently, microvascular endothelial cells of the blood-brain barrier were considered a homogeneous population, whose properties were induced by astrocytes. To address the question of brain endothelial cell heterogeneity, we measured the activity of specific markers of endothelial cells of different origins, including two brain-derived endothelial cell lines grown on plastic or on extracellular matrix (ECM) components secreted either by a glial or a fibroblast cell line, with or without the addition of astrocyte-conditioned medium (ACM).ECM components and ACM conjointly, but differently in each endothelial cell line, increased the uptake of leucine and modulated the expression of the specific markers alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGTP) in both cerebral endothelial lines. ACM decreased the incorporation of thymidine in the pulmonary endothelial cell line, but not in a cerebral cell line. An induction of blood-brain barrier specific GGTP was never observed in endothelial cells of non-cerebral origin.These results demonstrate that subpopulations of cerebral endothelial cells exist, that astrocyte-derived soluble factors and ECM components can modulate the expression and the function of markers of endothelial cells and that astrocyte-derived soluble factors have a selective growth inhibitory effect on endothelial cells of non-cerebral origin.

ISSN:1062-3329    

DOI:10.3109/10623329309102314

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The mitogenic effect of spheroids of the human colorectal cancer cell line HT29 on a monolayer of bovine capilarly endothelial cells was investigated to determine the relationship between aspects of three-dimensional tumor growth and endothelial cell mitogenesis. Spheroid-conditioned media caused a significant increase in the labeling index (LI) of endothelial cells over control values. An inverse relationship was found between the age of spheroids and their ability to produce endothelial mitogens. Young (day 5) spheroids induced a significantly higher LI in endothelial cells than more mature ones. The decrease in mitogenicity preceded the development of necrosis in the spheroids. Futhermore, conditioned medium from mature (day 21) spheroids suppressed the mitogenic activity from young spheroids to a significant degree, indicating that larger tumor nodules may produce inhibitors of endothelial cell proliferation. The model described here indicates that further studies with young and mature spheroids could provide important information on the regulating mechanisms exerted by growing tumor nodules on tumor-associated angiogenesis.

ISSN:1062-3329    

DOI:10.3109/10623329309102315

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The effect of severe hypoxia on the vascular tone of isolated rat aortic rings with and without endothelium was studied. Hypoxia induced transient contractions that were significantly more pronounced in preparations with endothelium. These responses were reproducible during two consecutive episodes of hypoxia. With increasing concentrations of phenylephrine (EC 10 to EC 100) the amplitude of endothelium-dependent hypoxic contractions decreased. Indomethacin, the inhibitor of cyclooxygenase, had no effect on hypoxic contractions whereas substances that decrease the cyclic GMP content of vascular smooth muscle cells (methylene blue, nitro-L-arginine) inhibited hypoxic contractions. M&B 22948, a substance that increases the cyclic GMP level, augmented hypoxic contractions. Low concentrations of exogenous donors of nitric oxide (sodium nitroprusside, SIN-1) caused the appearance or significantly augmented hypoxic contractions in preparations without endothelium. This was not observed with the cyclic AMP-dependent vasorelaxant isoproterenol. The measurement of cyclic GMP levels revealed low concentrations in rings without endothelium that increased significantly following stimulation with sodium nitroprusside under control oxygenation. Hypoxia caused a significant transient decrease in cyclic GMP levels. The activity of purified soluble guanylyl cyclase (basal and after stimulation with sodium nitroprusside) increased under hypoxic conditions compared to control oxygenation. These results suggest that hypoxic contraction in rat abdominal aorta is due to a decrease of cyclic GMP content in vascular smooth muscle that is probably not mediated through direct inhibition of guanylyl cyclase.

ISSN:1062-3329    

DOI:10.3109/10623329309102316

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The actions of ester and non-ester muscarinic antagonists on the acetylcholine-induced relaxation of phenylephrine-contracted endothelium intact rat aortic rings were investigated. Atropine, scopolamine and 4-diphenyI-acetoxy-N-methylpiperidine (4-DAMP) inhibited the relaxation in the nanomolar range, homatropine at 10−6M, pirenzepine at 10−6M, AFDX 116 at 10−5M while gallamine at 10−5M was without effect. Methyl-butyrate (10−4M) potentiated the inhibition by atropine and homatropine by one order of concentration and normalized the gradient to within 0.9–1.1 of the Schild regression for the two compounds. This was not observed with scopolamine. Our findings indicate that the endothelium of the rat aortic ring may contain an esterase that hydrolyses the tropine but not the scopine esters of the belladonna alkaloids. In addition, our data also show that the endothelial muscarinic receptor of the rat aorta is of the M3subtype. These findings may provide an explanation for our earlier binding study showing that endothelial muscarinic receptors have low affinity for atropine and homatropine.

ISSN:1062-3329    

DOI:10.3109/10623329309102317

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The role of endothelium in the mediation of dilation evoked by vasoactive agents in the microcirculation of rat mesentery and gracilis muscle has not been assessed directly and the results obtained so far are controversial. The aim of our study, therefore, was to investigate if changes occurred in the dilator responses of small, isolated arterioles (20 to 200μm) after physical removal of the endothelium. Isolated arterioles were visualized with television microscopy and diameters measured with an image-shearing device. Dilation of three different orders of rat mesenteric (193.5±7.0, 92.5±4.6, and 35.6±4.8μm respectively) and gracilis (76.9±1.6, 32.3±1.1, and 22.3±1.6μm) muscle arterioles was investigated in response to acetylcholine (ACh; 10−6M) and sodium nitroprusside (SNP; 10−7M or 5×10−8M) at constant intravascular pressures (100, 80 and 80/50 mm Hg, respectively). In the presence of the endothelium, all arterioles dilated (20–100%) in response to ACh and SNP. Endothelium removal was accomplished by infusing 1–2 ml air into the lumen of the arteriole. This resulted in a separation of the endothelium from the sub-endothelial layer which was than cleared from the lumen by perfusion with Krebs' solution. After removal of the endothelium, arterioles lost their ability to dilate in response to ACh, but retained their responsiveness to SNP. The basal tone of the two smaller order gracilis arterioles increased slightly after removal of the endothelium. These studies demonstrate that the endothelium can be removed from small arterioles of the mesentery and gracilis muscle of rats, and that the presence of endothelium is obligatory for the dilator response of arterioles to ACh, but not to SNP.

ISSN:1062-3329    

DOI:10.3109/10623329309102318

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Experiments were conducted to determine the effect of surgical preparation and infusion of plasma and/or saline on circulating immunoreactive endothelin (irET) concentrations. Male Sprague-Dawley rats anesthetized with Inactin were placed on a surgical heating table for about 2 h before collecting blood via puncture of the abdominal aorta. The plasma concentration of irET was 8.1±0.9 pg/ml in rats that did not undergo surgical preparation or receive any further treatment. Standard surgical preparation as for renal clearance experiments (catheters in the trachea, femoral artery, femoral vein, and bladder) resulted in a dramatic rise in irET to 17.7±3.0 pg/ml (p<0.05). Infusion of plasma (5 ml/kg over 20 min), but not saline, resulted in an additional increase to 32.6•3.5 pg/ml (p<0.05). These results clearly demonstrate that standard whole-animal techniques such as surgery and plasma infusion produce significant changes in circulating endothelin which may affect a variety of physiological and pharmacological mechanisms being investigated in the anesthetized rat.

ISSN:1062-3329    

DOI:10.3109/10623329309102319

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Recentin vitroandin vivostudies have demonstrated that the vascular endothelial cell layer covering the luminal surface of vessel walls is not a simple, non-thrombotic permeability barrier as previously thought. The cells have various unique functions and play many important roles in the regulation and remodeling of the entire vascular wall. One of the most noticeable findings in these studies is the fact that endothelial cells possess mechanisms for sensing hemodynamic forces, such as fluid shear stress induced by blood flow and circumferential tensile stress due to blood pressure. They alter not only their own morphology and functions but also those of smooth muscle cells and other tissues in the outer layer, according to the sensor information. However, the cellular mechanisms detecting and responding to these mechanical stesses are not well understood.

ISSN:1062-3329    

DOI:10.3109/10623329309102320

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor