摘要:

The importance of nitric oxide in the acute and long-term regulation of arterial pressure and renal function is supported by the results obtained in many studies. Reports described in this brief review provide evidences that nitric oxide plays an important role in regulating the urinary sodium and water excretion in basal conditions and during increments in arterial pressure and extracellular volume. Data showing an important interaction between nitric oxide and angiotensin II or prostaglandins in the regulation of the renal excretory function is also provided. These studies support the concept that the development of sodium sensitive hypertension could be secondary to a deficient nitric oxide production.

ISSN:1062-3329    

DOI:10.3109/10623329609024684

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

A direct correlation was observed between the invasive and metastatic potential of A375 melanoma cells and their expression of tenascin and ability to support endothelial cell adhesion and reorganization. Since the ability to metastasize and establish a neovasculature requires interaction of tumor cells with extracellular matrix and endothelial cells, we examined the potential of matrix proteins synthesized by three melanoma cell lines with low-A375P, medium-A375M and high-A375SM invasive and metastatic properties to induce adhesion and rearrangement of human umbilical vein endothelial cells (HUVECs) in vitro. HUVECs adhered to and reorganized into a network of connecting and aligned cells on wells conditioned by A375SM and A375M but not A375P cells. These changes in morphology suggested differences in matrix composition among the three melanoma cell lines. In comparison to low levels of substrate-bound fibronectin and laminin, increasingly higher levels of substrate-bound tenascin were synthesized by the A375P, A375M, A375SM cell lines. HUVEC adhesion and reorganization on A375-conditioned matrix was tenascin-dependent and could be inhibited with antibodies against human tenascin. HUVEC adhesion to A375SM-conditioned matrix and tenascin requireαV.β3while reorganization may requireα2β1 as well. Our results suggest that tenascin plays a role in integrin-dependent adhesion and reorganization of HUVECs in response to the extracellular matrix of metastatic melanoma cells.

ISSN:1062-3329    

DOI:10.3109/10623329609024685

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Nitric oxide is synthesized by vascular smooth muscle cells in response to endotoxin or inflammatory mediators. We investigated the molecular basis for the induction of nitric oxide synthase (NOS) in response to lipopolysaccharide (LPS) or IL-1βusing rat vascular smooth muscle cells derived from pulmonary and systemic vasculature. The regulation of mRNA levels for this enzyme in response to LPS or IL-1βtreatment was examined in parallel with changes in levels of cyclic GMP. We found an increase in expression of inducible NOS transcript corresponding to an increase in cyclic GMP levels beginning with 3 hr of exposure to either LPS or IL-Iβ. In cells derived from the pulmonary circulation, initial induction of NOS transcript was detectable at 3 hr and the transcript levels continued to increase to a maximum level at 24 hr. In contrast, the cells derived from the systemic vasculature showed a maximal induction of NOS transcript at 3 hr, and the level decreased from this time point to 24 hr. The full induction of NOS transcripts was dependent on new protein synthesis and on cellular tyrosine protein kinax activity. Thus, the production of nitric oxide in vascular smooth muscle cells in response to either LPS or IL-1βresults from increased expression of the gene for (inducible) NOS. The pathways by which either of these two agents induce the nitric oxide synthase gene, however, are distinct.

ISSN:1062-3329    

DOI:10.3109/10623329609024686

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Confluent monolayers of cultured retinal microvascular endothelial cells (RVEC's) were exposed simultaneously to two different protein-gold conjugates to determine if partitioning or sorting of protein ligands occurs during receptor mediated endocytosis in CNS microvascular cells. A mixture of bovine serum albumin (BSA), conjugated with 5nm colloidal gold (BSA-gold) and transferrin (TO, conjugated with 15nm gold (Tf-gold) were added to RVEC's and the monolayers processed,in situ, for TEM. At 0 mins the gold conjugates bound diffusely to the apical plasma membrane, but after 2 mins, both ligands were observed to cluster in clathrin-coated pits prior to internalisation in coated vesicles. At 5 mins the gold-ligands were co-localised in coated vesicles and early endosomes. After 10 mins the probes were observed in larger late endosomes where segregation was first noted and by 30mins, the mixture of gold particles appeared partitioned within late endosomes, with BSA-gold localised at the periphery and Tf-gold bound to tubular membranes of the organelle. At>30min incubation, BSA-gold was occasionally observed in presumptive lysosomes although, more frequently, both ligands appeared separately as discrete aggregates at the basal membrane. These results indicate that RVEC's have the ability to intemalise, segregate and ultimately exocytose complex mixtures of blood-borne macromolecules.

ISSN:1062-3329    

DOI:10.3109/10623329609024687

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Stimulation of endothelial nitric oxide production by bradykinin or the angiotensin converting enzyme inhibitor“ramiprilat”has been indirectly assessed in terms of intracellular cyclic GMP accumulation. However, direct measurement of endothelial nitric oxide synthesis and release has not been analyzed. Using a selective porphyrinic microsensor, nitric oxide release was detected from single primary cultured bovine aortic endothelial cells. Maximal nitric oxide release of 540±38 or 122±10 n mol/L was achieved by bradykinin at 5×10−8mol/L or by ramiprilat at 10−7mol/L respectively. The time course of nitric oxide release by bradykinin showed a rapid initial production rate (22.5±1.6 nmol/L/sec, 4.2% increase per second) and was transient within 15 min (decay rate 0.60±0.05 nmol/L/sec). In contrast, the initial production rate of nitric oxide release by ramiprilat was slow (0.34±0.03 nmol/L/sec, 0.28% increase per second) and reached a plateau level after 6 min, which remained stable for at least 14 min. Maximal nitric oxide release induced by bradykinin was immediately blocked by the kinin receptor antagonist“icatibant”(Hoe 140). The subsequent decay rate of nitric oxide was 8.0±1.4 nmol/L/sec. In comparison, the inhibitory effect of icatibant on ramiprilat-induced nitric oxide release revealed a decay rate of nitric oxide which was 1/6 as fast. These data, especially the different kinetics of both compounds, which are quite similar to previously reported data for intracellular cyclic GMP accumulation in the same cells provide strong evidence that endothelial cyclic GMP can be considered as an index for nitric oxide generation.

ISSN:1062-3329    

DOI:10.3109/10623329609024688

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

We report here that exposure of large vessel EC to clinically relevant, atherogenic levels of native LDL (240 mg cholesterol/dL) increases the incidence and severity of shear-induced EC plasma membrane wound injuryin vitro.The proportion of LDL-treated EC that survived mechanical shearing in suspension was significantly less (∼20%; p<0.005) than that of control, untreated EC. Moreover, the amount of a fluorescent, cytoplasmic wound marker, detected by flow cytometry, in surviving LDL-treated cells was significantly more (∼2 log units; p<0.005) than that detected in surviving, control EC. Mechanically sheared LDL-treated EC released significantly more (∼2 fold; p<0.02) bFGF than sheared, control EC. LDL treatment of EC resulted in an increase of∼60% in membrane-associated cholesterol, and an increase in the cholesterol/phospholipid ratio from 0.6 to 1.3. Fluorescence anisotropy revealed that the plasma membrane fluidity (PMF) of LDL-treated EC was significantly lower than that of control EC. When the PMF of LDL-treated EC was raised using the membrane fluidizing agent, A2C, we observed a significant reduction in EC vulnerability to shear stress, whereas the presence of the membrane ordering agent, PF-68, caused a significant increase in LDL-treated EC vulnerability to shear stress. Our data suggest that LDL-induced increases in EC vulnerability to mechanical stress and consequent bFGF release, may promote EC injuryin vivo, and hence promote the initiation of atherogenesis.

ISSN:1062-3329    

DOI:10.3109/10623329609024689

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

A genetic model of cardiomyopathy, the Syrian cardiomyopathic hamster, is characterized by myocardial necrosis and dysfunction which may be initiated by inadequate coronary blood flow. The mechanisms mediating coronary vasospasm observed during the development of cardiomyopathy in this model are unknown. The present study utilized isolated coronary arteries (150-250 pm diameter) from cardiomyopathic (M) and Golden Syrian control (C) hamsters to determine if endothelial dysfunction was present during the necrotic stage of cardiomyopathy (60-90 days of age). Intraluminal diameter was continuously recorded in coronary arteries maintained at an intraluminal pressure of 40 mxnhg. In pre-constricted vessels, relaxation to the endothelium-dependent vasodilator, acetylcholine (ACh), was impaired in vessels from M compared to C hamsters. Inhibition of nitric oxide synthase activity with N-nitro-L-arginine (LNA) significantly reduced relaxation to ACh in coronary arteries from C hamsters. However, LNA had little effect on relaxation to ACh in coronary arteries from M hamsters. Relaxation to endothelium-independent vasodilators, nitroprusside or isoproterenol, was similar in coronary arteries from both C and M hamsters. Superoxide dismutase (SOD) restored relaxation to ACh in coronary arteries of M hamsters, but did not alter relaxation to ACh in coronary arteries from C hamsters. In summary, relaxation to ACh is reduced and is primarily mediated by a substance other than nitric oxide in coronary arteries from M compared to C hamsters. Additionally, superoxide anions contribute to impaired endothelium-dependent coronary artery relaxation to ACh in young M hamsters. This impaired coronary relaxation may accentuate coronary vasospasm during the development of cardiomyopathy.

ISSN:1062-3329    

DOI:10.3109/10623329609024690

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

We studied the effects of endothelin family peptides on the pumping responses of lymphatic vessels, the receptors involved and whether vessel-derived endothelin played a role in the myogenic response to changes in transmural pressure. Postnodal bovine mesenteric lymphatics were suspended in an organ bath preparation with both inflow and outflow ends cannulated. Input to the ducts was provided from a reservoir filled with Krebs solution. With a 6 cm H2O fixed transmural pressure applied to the vessels to initiate spontaneous contractions, ET-1, ET-2 and ET-3 (tested between 10−10and 10−8PM) depressed lymphatic pumping in a concentration-dependent fashion with the order of potency being ET-1 = ET-2>ET-3. The concentrations of ET-1 and ET-2 that depressed pumping 50% were 0.96×10−9M and 0.95×10−9M respectively. Similarly, when transmural pressures were varied in 2 cm H2O increments between 0 and 14 cm H2O, ET-1 at 10−9and 10−8M significantly depressed fluid pumping at the majority of distending pressures tested. The ET(A) receptor antagonists BQ 123 and BQ 610 blocked the effects of ET-1. The ET(B), antagonist BQ 788 was a less effective antagonist. We could find no evidence that endogenous endothelin played a role in the myogenic response as the ET(B), or ET(B)receptor antagonists (alone or combined) had no effect on the spontaneous pumping induced by the application of transmural pressure. These results demonstrated that endothelin is a potent inhibitor of pumping activity in bovine lymphatic vessels. This effect appears to be mediated largely by ET(A)receptors.

ISSN:1062-3329    

DOI:10.3109/10623329609024691

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Cyclosporine A is an efficient immunosuppressive agent, however, its use is associated with complex alterations of vascular tone. Numerous clinical and experimental observations indicate acute and chronic effects of cyclosporine A that are modulating endothelial and vascular smooth muscle function. Cyclosporine A impairs the vasodilator function of the endothelium; at the vascular smooth muscle contractions to angiotensin II are augmented, whereas conflicting results were obtained with other vasoconstrictors. Furthermore, cyclosporine A may alter circulating and locally released vasoactive hormons, such as renin/angiotensin II, catecholamines and endothelin-1. The cellular mechanisms mediating the effects of cyclosporine A in the arterial wall are not completely understood, but several experimental findings give a more and more detailed picture of potentially involved systems.

ISSN:1062-3329    

DOI:10.3109/10623329609024692

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor