摘要:

17β-estradiol exhibits vasculoprotective effects in vivo. This has been supported by earlier and recent epidemiological data demonstrating greater incidence of atherosclerosis, coronary artery diesease, myocardial infarction, hypertension and other major cardiovascular diseases in man and postmenopausal women compared to premenopausal females. The mechanism(s) of vasculoprotection by estrogens is not known. Presence of the estrogen receptor in the vascular wall makes it feasible that estrogen could exert direct vascular effects and could contribute to the regulation of the cardiovascular system. Nitric oxide, synthesized under physiological conditions by the vascular endothelium, participates in a wide variety of vasculoprotective processes. Based on current evidence from the literature the endothelial constitutive nitric oxide synthase could be a potential target of estrogen's vascular action and may contribute to vasculoprotection by the female sexual steroid hormone.

ISSN:1062-3329    

DOI:10.3109/10623329409053376

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Cultured vascular endothelial cells demonstrate procoagulant activity following stimulation by cytokines and other inflammatory agents. Tissue factor is a cell surface membrane protein, which functions as a receptor and essential cofactor for Factor VII triggering the blood coagulation process. The mechanism(s) by which cytokine/inflammatory agents stimulate the production of tissue factor is still unclear. We hypothesized that protein kinase C (PKC) may be involved in cytokine/inflammatory agent-induced up-regulation of tissue factor in human vascular endothelial cells. The production of tissue factor by human umbilical endothelial cells (HUVEC) was enhanced markedly (5-10 fold) by TNFα(100 U/ml), IL-1 (10 U/ml) or LPS (100 ng/ml). Phorbol esters (PMA or PDBu) stimulated the production of tissue factor by HUVEC in a concentration-dependent manner, while the biologically inactive analog of PDBu, 4α-PDBu was inactive. Maximal stimulation by PMA (10-12 fold) was obtained at 200 nM and the ED50was 50 nM. PDBu was 10 times less active than PMA with an ED50of 500 nM. The non-phorbol activator of PKC, octylinolactam V also stimulated the production of tissue factor in a concentration-dependent manner and maximal stimulation (15 fold) was obtained at 3μM. Octylindolactam V-, cytokine-, or LPS-stimulated tissue factor production was blocked (50-100%) by the relatively selective PKC inhibitor H-7 (10-30μM). The rank order potencies of various kinase inhibitors tested on TNFα-induced tissue factor production was staurosporine>calphostin C>H-7>HA 1004 = H-8. The present study provides evidence for the involvement of endothelial PKC in cytokine-induced up-regulation of tissue factor production.

ISSN:1062-3329    

DOI:10.3109/10623329409053377

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

We have cloned a cDNA encoding rat neutrophil inducible nitric oxide synthase (iNOS). The amino acid sequence of the iNOS in the rat neutrophils was 95% identical to that in the mouse macrophages, and the difference between the two sequences was most likely the result of species variability. Moreover, the iNOS in the rat neutrophils was 99% identical in amino acid sequence to that in the rat hepatocytes and vascular smooth muscle cells (VSMC). Northern blot analysis of total RNA from both rat macrophages and neutrophils showed a single band above 4 kilo-nucleotides. These findings suggest that iNOS in rat neutrophils, macrophages, hepatocytes, and VSMC are almost identical in the primary structure.

ISSN:1062-3329    

DOI:10.3109/10623329409053378

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Although studies suggest that endothelin (ET) meditates vasoconstriction associated with post-ischemic acute renal failure (ARF), the effect of ischemia on endothelin receptors is equivocal. In the current study, the left renal artery in Sprague-Dawley rats was occluded for 60 min to induce ARF. Animals were allowed to recover and whole kidneys were removed 24 h later to prepare membranes for binding studies. Binding studies indicate that the left ischemic kidney displayed more [251I]ET-1 binding than the non-ischemic right kidney. Values of Bmaxand KDwere 159±33 fmol/mg and 545±137 pM vs. 272±35 fmol/mg of protein and 638±120 pM for right and left kidneys, respectively (n = 5). Both right and left kidneys from sham-operated rats exhibit similar B., and KD values (126±17 fmol/mg and 365±36 pM vs. 152±20 fmol/mg and 472±48 pM, n = 4). Similar results were obtained for ET-3 binding. No significant difference was observed for tissue concentrations of ET between the right and left kidneys. Although the wet weight was not significantly different, the protein content of ischemic kidneys were 33% less than that of non-ischemic kidneys. These results suggest that ET receptors may be up-regulated in post-ischemic kidneys. Alternatively, ET receptors may be expressed in regions of the kidney that are less susceptible to ischemia-induced tissue damage.

ISSN:1062-3329    

DOI:10.3109/10623329409053379

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Conflicting data have been reported for the role of endothelium-derived relaxing factor (EDRF) in the control of renin release from juxtaglomerular (JG) cells of the kidney. We have examined, in the isolated perfused rat kidney, how renin secretion is influenced by inhibitors or stimulators of EDRF, as well as by nitric oxide-generating drugs. Acetylcholine (15 nM) or carbachol (5μM) stimulated renin release. These effects could be attenuated by N-nitro-L-arginine (L-NNA, 20μM) or N-monomethyl-L-arginine (L-NMMA, 50μM).When given alone, these inhibitors of NO-synthase reduced basal renin release by 30-60%. Infusion of L-arginine (2 mM), the precursor of EDRF, stimulated renin release, restored L-NNA-inhibited renin release and prevented inhibition by L-NMMA. The NO-generating sydnonimine SIN-1 (2μM), induced an increase in renin release, which was not altered by L-NNA. In hydronephrotic rat kidneys lacking tubular structures, N-nitro-arginine methylester (L-NAME, 20μM) inhibited, while carbachol (1μM), SIN-1 (10μM) and sodium nitroprusside (5μM) stimulated renin release, indicating that the effects of these agents on renin release do not depend on tubular mechanisms. It is concluded that EDRF is a stimulator of renin release with a direct action on JG-cells.

ISSN:1062-3329    

DOI:10.3109/10623329409053380

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

The role of endothelial cell anionic surface charge in the function of the blood-nerve barrier (BNB) was investigated in 16 Sprague-Dawley male rats. The polycation protamine sulphate (PS) was administered parenterally in 8 animals to neutralize the endothelial anionic charge. The effect of such neutralization on the permeability of the BNB to intravenously injected horseradish peroxidase (HRP), and on anionic sites labelling with cationic colloidal gold (CCG) and cationic ferritin (CF) were studied qualitatively and quantitatively. Eight control animals were similarly studied after parenteral administration of saline or buffer instead of PS. PS-treated animals showed a pronounced opening of the BNB to HRP, and a significant reduction of endothelial cell surface labelling with cationic probes. The association of a reduction in anionic sites with the breakdown of the BNB supports the view of an endothelial surface charge filter acting as a contributing factor to the normal function of the BNB. The possible role of charge in transcellular and paracellular transport routes is discussed.

ISSN:1062-3329    

DOI:10.3109/10623329409053381

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Prostaglandin (PG) I2causes vasoconstriction in isolated blood vessels and yet lowers blood pressure. This study was conducted to study the vascular effects of PGE2on isolated vascular tissues. PGE2(10–2000 ng/ml) caused a concentration-dependent contraction of quiescent rat aortic rings, and the contraction was greater in endothelium-denuded than in endothelium-intact rings. PGE2-induced contraction was also enhanced by prior treatment of quiescent endothelium-intact rat aortic rings with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), or the nitric oxide inactivator oxyhemoglobin. PGE2also caused an additional contraction of norepinephrine (NE)-precontracted rat aortic rings, but the additional contraction was similar in endothelium-intact or de-endothelialized rings. Pretreatment of endothelium-intact NE precontracted rings with L-NAME, or oxyhemoglobin, or the endothelin A and B receptors antagonist PD-142,893, or the cyclooxygenase inhibitor indomethacin did not affect the PGE2-induced contraction. On the other hand, pretreatment of endothelium-intact and denuded rings with the thromboxane A2/endoperoxide receptor antagonist SQ29548 almost completely abolished the PGE2-induced contraction. These observations indicate that the contractile effects of PGE2on quiescent rat aortic rings are endothelium-affectable, dependent but independent of endothelial integrity or function in NE-precontracted rings. Lastly, PGE2appears to cause contraction of rat aortic rings via activation of thromboxane A2/endoperoxide receptors on vascular smooth muscle cells.

ISSN:1062-3329    

DOI:10.3109/10623329409053382

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Interendothelial junctions in continuous endothelium are the primary pathway for the passage of fluid, solutes, and leukocytes from the intravascular compartment to the interstitium. The maintenance of these channels is in part a function of circulating metabolites and local secretions produced by the cells of the microvessel wall. When this regulatory mechanism is disrupted, such as in an acute inflammatory response, interendothelial gaps appear and the microvascular barrier is compromised. Glycosylated cell surface proteins are believed to play a role in the development and maintenance of junctional apposition, and hence permeability. A predictable response of microvascular endothelial cells to an inflammatory stimulus therefore should be a change in junction-associated glycoproteins. Moreover, the heterogeneity of microvascular endothelial barrier properties may in part be a function of specific glycans involved in cell-cell contact. To test these suppositions, the binding of a panel of lectins to cultured endothelial and mesothelial cells is observed and compared under resting and stimulated (with the inflammatory agonist thromboxane) conditions. The binding of wheat germ agglutinin to cell borders is greater than for other lectins tested in both endothelial and mesothelial cell cultures. After confluence, binding sites at the junction disappear in endothelial cells but remain in mesothelial cells. A thromboxane-mimic (CTA2) induces gap formation, a redistribution of wheat germ agglutinin binding sites and an increase in intercellular permeability. These changes correlate with our published studies on the time and extent of endothelial contractions and corresponding increased permeability of an EC monolayer induced by thromboxane and other inflammatory agents.

ISSN:1062-3329    

DOI:10.3109/10623329409053383

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:1062-3329    

DOI:10.3109/10623329409053384

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor