Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytokine interleukin-1 (IL-1) has a variety of effects in the kidney involving induction of nephritis and renal injury. In addition, recent reports suggest that IL-1 regulates natriuresis and renin secretion in the kidney. To examine the potential sites of action of IL-1 in the kidney, we used iodine-125-labeled recombinant human interleukin-1 alpha ([125I]IL-1 alpha) to identify and characterize IL-1 receptors in crude membrane preparations of mouse (C57BL/6) kidney. The binding of [125I] IL-1 alpha was linear over a broad range of membrane protein concentrations, saturable, reversible, and of high affinity, with an equilibrium dissociation constant (Kd) of 66 +/- 10 pM and a maximum number of binding sites of 1.04 +/- 0.24 fmol/mg protein. In competition studies, recombinant human IL-1 alpha, recombinant human IL-1 beta, and a weak IL-1 beta analog (IL-1 beta+) inhibited [125I]IL-1 alpha binding to mouse kidney in parallel with their relative bioactivities in the T-cell comitogenesis assay, with inhibitory binding affinity constant (Ki) values of 28 +/- 19, 53 +/- 23, and 5560 +/- 2098 pM, respectively; rat/human CRF and human tumor necrosis factor had no effect on [125I]IL-1 alpha binding. In autoradiographic studies, IL-1 receptors were heterogeneously distributed in the kidney, with significantly higher densities present in the medulla than in the cortex. To study the effects of endogenous IL-1 in modulating [125I]IL-1 alpha-binding sites in kidney, we injected 30 micrograms of the bacterial endotoxin lipopolysaccharide (LPS) to mice ip. Autoradiographic studies demonstrated substantial decreases in [125I]IL-1 alpha binding in both the kidney cortex (control, 34.7 +/- 6.2 fmol/mg tissue equivalent; LPS, 11.3 +/- 0.3; P less than 0.05) and medulla (52.7 +/- 8.1 vs. 26.0 +/- 1.0; P less than 0.05) 24 h after injection of LPS. Saturation studies in whole kidney homogenates demonstrated that the LPS-induced decrease in [125I]IL-1 alpha binding was primarily due to a down-regulation of IL-1 receptors (i.e. decrease in the maximum number of binding sites). The identification of IL-1 receptors in kidney with characteristics similar to those of IL-1 receptors in the brain-endocrine-immune axis provides further support for a physiological role for IL-1 in regulating renal function.
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PMID:Interleukin-1 receptors in mouse kidney: identification, localization, and modulation by lipopolysaccharide treatment. 182 79

Angiotensinogen is the precursor of biologically active peptide angiotensin II and its hepatic synthesis is increased by the induction of acute inflammation. Studies were carried out to know whether the rise in plasma angiotensinogen is actually involved in the activity of the renin-angiotensin system during acute inflammation. The plasma level of angiotensinogen in rats was increased to 2.5 times the normal level 16 h after the induction of acute inflammation by administration of lipopolysaccharide (LPS). The plasma renin concentration (PRC) was decreased to about 40% of the normal level concomitantly with a reduction of plasma renin activity (PRA) at 4 h after LPS administration. In contrast, 16 h after LPS injection, when plasma angiotensinogen showed a high level and PRC had recovered to the normal range, PRA was increased to 1.7 times the normal level. These results indicate that acute inflammation induced by LPS causes a biphasic change in the generation of angiotensin I, i.e., an early decrease depending upon the reduction of PRC and later increase depending upon elevation of the angiotensinogen concentration.
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PMID:Changes in activity of the renin-angiotensin system of the rat by induction of acute inflammation. 264 7

Febrile, endocrine, and renal responses to i.v. injection of endotoxin (E. coli lipopolysaccharide, 0.25 microgram kg-1) were studied in hyperhydrated goats without, and after dexamethasone pre-treatment, performed with the aim of inhibiting the adenohypophyseal secretion of ACTH. As expected from previous investigations, the administration solely of endotoxin induced biphasic fever, pronounced and long-lasting (less than 4 h) elevation of plasma cortisol (PC), and a prompt inhibition of the water diuresis. Apparently the observation that endotoxin also induced a pronounced biphasic elevation of plasma aldosterone (PA) where the two rising phases coincided with the early, and respectively the second elevation in rectal temperature is original. The endotoxin had no obvious influence upon the renal Na excretion for 3 h post-injection, and did not affect plasma renin activity (PRA). After dexamethasone pre-treatment (0.02 mg kg-1, i.v. 75 min prior to endotoxin) the endotoxin-induced rise in rectal temperature initially was less steep and no biphasic pattern of the fever was observed. The PC and antidiuretic responses became delayed for about 2 h and were then much attenuated. Endotoxin-induced rise in PA was no longer observed, and a conspicuous natriuresis developed within 90 min post-endotoxin. It is concluded that endotoxin at the dose used causes liberation of ACTH to such an extent that adrenocortical hypersecretion not only of glucocorticoids, but also of aldosterone occurs. The observed differences in Na excretion suggest that this aldosterone hypersecretion may be of pathophysiological importance as a protection against inappropriate renal waste of Na during the early phase of endotoxin-induced fever.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ACTH-mediated aldosterone hypersecretion during endotoxin-induced fever with apparent influence upon renal sodium excretion. 303 75

The effect of different experimental models of inflammation on plasma concentrations of T-kininogen and angiotensinogen was examined in the rat. T-kininogen, a major phase protein which inhibits cysteine proteinase is increased in all cases of induced inflammation: administration of lipopolysaccharide and turpentine, bilateral nephrectomy or sham-operation and intraperitoneal injection of peanut oil. Angiotensinogen, the renin-substrate, is increased by lipopolysaccharide but is decreased by turpentine. Sham-operation or peanut oil injection have no effect on angiotensinogen whereas, bilateral nephrectomy and dexamethasone increase its concentration. Therefore, angiotensinogen is regulated differently than T-kininogen during inflammation.
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PMID:Differential effects of inflammation models on rat T-kininogen and rat angiotensinogen. 328 77

As4.1 cells are derived from a renin-expressing kidney tumor induced by tissue-specific oncogene-mediated tumorigenesis in transgenic mice. These cells express high levels of renin messenger RNA (mRNA) and synthesize prorenin and renin; they were therefore used as a model to further investigate the molecular biology of renin-producing kidney cells by cloning and characterizing novel mRNAs expressed in these cells. One clone, designated 1.5, was randomly selected from an As4.1 complementary DNA (cDNA) library, and two other cDNA clones, designated 4.9 and 6.9, were obtained by screening the cDNA library using a strategy to identify As4.1 cell-specific mRNAs. Each clone exhibited a highly restricted tissue-specific expression profile, including high level expression in As4.1 cells and low level expression in kidney. No homology was found between the sequence of the partial 1.5 and 4.9 cDNAs and sequences in Genbank. Southern blot analysis revealed that clone 4.9 is encoded by a single copy gene containing at least two separate exons. A homology search of the sequence of clone 6.9 revealed it to encode a cDNA to serum amyloid A protein; consistent with this identification, expression of 6.9 mRNA was highly induced in both kidney and liver after treatment of mice with Escherichia coli lipopolysaccharide.
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PMID:Tissue-specific expression of novel messenger ribonucleic acids cloned from a renin-expressing kidney tumor cell line (As4.1). 778 30

Although various mediators such as platelet activating factor, anaphylatoxin and cytokines are considered to be involved in the pathology of endotoxin-induced shock, an endothelium-derived relaxing factor (EDRF), nitric oxide (NO) or its related substance, has recently been shown as a vasodilating factor that is produced from L-arginine. On the other hand, NG-nitro-L-arginine (L-NNA) is shown to inhibit NO production from L-arginine. Thus, in order to examine a possible involvement of NO in the shock, the effect of L-NNA administration was studied on the hemodynamics and plasma hormone levels during endotoxin-induced shock in anesthetized dogs. Twenty-five mongrel dogs were divided into the following 5 groups; (1) In group C, only physiological saline was administered. (2) In group L, a bolus injection of L-NNA (4 mg/kg B.W.) was followed by a continuous infusion of the agent (0.05 mg/kg B.W./min) for 120 min. (3) In group E, lipopolysaccharide (LPS) E. Coli 011:B4 2.625 mg/kg body weight was administered. (4) In group LE, L-NNA administration (bolus and continuous) the same as in group L was started 5 min before the injection of LPS. (5) In group EL, L-NNA administration (bolus and continuous) was started 5 min after the injection of LPS. In Group LE, MAP decreased to -45.9 mmHg 5 min after LPS injection and -33.0 mmHg 120 min from pre-level. The levels of MAP from 15 to 90 min were significantly higher than those in Group E. In Group EL, MAP decreased to -61.4 mmHg 5 min after LPS injection and this low level (-59.5 mmHg) continued for 120 min. A protecting effect of L-NNA against LPS-induced hypotension was clearly observed only when administration of the agent was started before LPS injection. These results indicated that LPS induced shock could be produced by a possible increase of NO production in the vascular endothelial cells. The other finding in the present experiment using anesthetized animals was that L-NNA had a stimulatory action on some endocrine systems such as the renin-aldosterone system and pituitary-adrenal axis, although the exact mechanism of this action of L-NNA on such systems was unclear.
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PMID:[The effect of NG-nitro-L-arginine administration on the hemodynamics and plasma hormone levels during endotoxin shock in dogs]. 838 33

Previous studies in adult animals have indicated that plasma angiotensin converting enzyme (ACE) activity is inhibited by endotoxin. Reduced ACE activity may decrease plasma angiotensin II (AII) levels, contributing to the refractory hypotension we have previously reported in neonatal septic shock. In this study, hemodynamic function, plasma renin activity (PRA), AII, prostacyclin (PGI2), and thromboxane B2 (TxB2) levels were measured in 17-20-day-old dogs before and 1, 2, and 3 hr after endotoxin administration (1 mg/kg, Escherichia coli lipopolysaccharide-B). PRA and AII levels rose significantly 60 min post-endotoxin, returning to baseline values by 180 min; PGI2 and thromboxane B2 levels rose post-endotoxin and remained elevated. Indomethacin or captopril was given by oral gavage 30-35 min before endotoxin. Captopril significantly blunted the rise in PRA and AII, while indomethacin blocked the rise in PGI2 and TxB2. Mean arterial blood pressure and cardiac output fell 60 min after endotoxin challenge without pharmacologic intervention and remained depressed. Our data suggest that renin and AII responses to endotoxin challenge remain intact in the neonatal subject. Maintenance of hemodynamics in indomethacin-pretreated dogs may be due to unopposed stimulation of the peripheral vasculature by AII. Thromboxane B2 in maintenance of vasomotor tone may be minimal in the young.
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PMID:Role of angiotensin II in neonatal sepsis. 850 19

It was found in acute experiments on white rats that injection of Salmonella typhimurium lipopolysaccharide activates renin-angiotensin-aldosterone system (RAAS) and causes oligohydruria form of acute renal failure (ARF). Enalapril, angiotensin-converting enzyme, being injected simultaneously with endotoxin, increases diuresis, glomerular filtration rate, electrolytes excretion and reabsorption by proximal tubules, decreases proteinuria and blood nitrogen-down to the normal. Thus, RAAS takes part in endotoxemia ARF induction and enalapril has protective effect.
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PMID:[The participation of the renin-angiotensin-aldosterone system in the pathogenesis of acute kidney failure in endotoxemia]. 881 32

Nitric oxide produced in endothelial cells affects vascular tone. To investigate the role of endothelial nitric oxide synthase (eNOS) in blood pressure regulation, we have generated mice heterozygous (+/-) or homozygous (-/-) for disruption of the eNOS gene. Immunohistochemical staining with anti-eNOS antibodies showed reduced amounts of eNOS protein in +/- mice and absence of eNOS protein in -/- mutant mice. Male or female mice of all three eNOS genotypes were indistinguishable in general appearance and histology, except that -/- mice had lower body weights than +/+ or +/- mice. Blood pressures tended to be increased (by approximately 4 mmHg) in +/- mice compared with +/+, while -/- mice had a significant increase in pressure compared with +/+ mice (approximately 18 mmHg) or +/- mice (approximately 14 mmHg). Plasma renin concentration in the -/- mice was nearly twice that of +/+ mice, although kidney renin mRNA was modestly decreased in the -/- mice. Heart rates in the -/- mice were significantly lower than in +/- or +/+ mice. Appropriate genetic controls show that these phenotypes in F2 mice are due to the eNOS mutation and are not due to sequences that might differ between the two parental strains (129 and C57BL/6J) and are linked either to the eNOS locus or to an unlinked chromosomal region containing the renin locus. Thus eNOS is essential for maintenance of normal blood pressures and heart rates. Comparisons between the current eNOS mutant mice and previously generated inducible nitric oxide synthase mutants showed that homozygous mutants for the latter differ in having unaltered blood pressures and heart rates; both are susceptible to lipopolysaccharide-induced death.
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PMID:Elevated blood pressures in mice lacking endothelial nitric oxide synthase. 891 64

All the angiotensin peptides originate from angiotensinogen, a glycoprotein synthesized by several tissues, including the brain and the anterior pituitary. In the rat, immunohistochemistry has been used to localize angiotensinogen in gonadotropes and in uncharacterized cells surrounding sinusoids. Both cell types are capable of secreting angiotensinogen in cell culture; only the gonadotropes contain angiotensin II (AngII) and are capable of secreting it in culture. It has been asserted that the perisinusoidal cells are the only source of angiotensinogen for the generation of AngII by gonadotropes. Our current data favor the existence of a complete intracellular renin-angiotensin system (RAS) in gonadotropes and a separate extracellular system which utilizes the high concentration of angiotensinogen from perisinusoidal cells. Furthermore, we postulate that gonadotrope AngII serves mainly reproductive functions, while the proximity of angiotensinogen-secreting cells to folliculostellate cells, and their access to the intercellular sinusoidal and follicular spaces, places the extracellular RAS in a strategic position to affect pituitary growth and the mediation of acute-phase immune responses. In the rat brain, angiotensinogen is expressed by the 16-18th day of fetal life and by areas generally concerned with vasopressor, electrolyte, and fluid homeostasis. Antisense deoxyoligonucleotides to angiotensinogen mRNA lower blood pressure in hypertensive rats and inhibit in vitro growth of neuroblastoma cells, indicating a significant role for angiotensinogen in mitogenic and homeostatic functions. It is commonly agreed that astrocytes express angiotensinogen. Neuronal angiotensinogen has also been demonstrated by immunohistochemistry, as a secretion from neuronal cell cultures, and by reverse-transcriptase polymerase chain reaction. The fate of secreted astrocytic and neuronal angiotensinogen remains obscure. Angiotensinogen is regulated in a tissue-specific manner with smaller or absent responses observed for brain tissue. By using astrocyte and neuronal cultures the actions on angiotensinogen production of growth hormone, IGF-1, inflammatory lipopolysaccharide, and phorbol ester have been examined. Recent observations show that angiotensinogen is regulated positively or negatively by glucocorticoids and that a positive synergism between cAMP and glucocorticoids exists. On the basis of analogous systems for other proteins, a scheme involving glucocorticoid receptors, CREB, and AP-1 transcription factors is formulated to explain glucocorticoid-cAMP interactions. These transcriptional interactions may form a significant functional link between the RAS and adrenergic mechanisms.
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PMID:Novel perspectives on pituitary and brain angiotensinogen. 910 Dec 59


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