Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate the roles of angiotensin II (Ang II) receptor subtypes 1 (AT1) and 2 (AT2) in producing vascular wall hypertrophy and qualitative changes in smooth muscle cell gene expression. Wistar rats were treated for 23 days with osmotic minipumps containing solvent and either Ang II (120 ng.kg-1.min-1) or PD123319 (30 mg.kg-1.d-1), an AT2 receptor antagonist. In addition, rats receiving solvent and either Ang II or PD123319 were given losartan, an AT1 receptor antagonist, in the drinking water (10 mg.kg-1.d-1). Vascular wall hypertrophy and smooth muscle phenotype were characterized by morphometric analysis combined with immunohistochemistry. Ang II-induced hypertension was associated with the development of medial hypertrophy of the aorta and coronary arteries accompanied by reversion of vascular smooth muscle cells (VSMCs) toward an immature phenotype, as shown by the expression of cellular fibronectin and nonmuscle myosin. Losartan treatment, which restored normal arterial pressure, prevented all these changes. PD123319 treatment, which had no effect on blood pressure, prevented only vascular hypertrophy, with no effect on VSMC phenotype. Administration of only losartan to normal rats reproduced the Ang II-induced vascular hypertrophy, with no effect on VSMC phenotype. Taken together, these results suggest that (1) the trophic effect of Ang II on VSMCs is mediated via AT2 receptor subtypes and (2) changes in VSMC phenotypes are triggered mainly through AT1 receptor subtypes.
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PMID:Differential roles of AT1 and AT2 receptor subtypes in vascular trophic and phenotypic changes in response to stimulation with angiotensin II. 908 79

Studies on fibronectin, endothelin-1, and mortalin from our laboratory are reviewed here. Fibronectin expression has been analyzed as upregulated during in vitro serial passaging of human fetal lung and neonatal foreskin fibroblasts as well as umbilical vein endothelial cells. In vivo aging of skin fibroblasts, as well as aortic endothelial cells, are also accompanied by upregulation of fibronectin expression. Fibronectin promoter binding proteins from young and old cell nuclear extracts were further explored by gel retardation assay. Preliminary analyses have detected age-related differential binding activities with respect to AP-1, CRES, TFIID, CTF, and AP-2 regions, whereas Sp1 binding proteins remain unaltered. Endothelin-1 expression is also seen as upregulated during in vitro and in vivo aging of endothelial cells. This can contribute to the hypertension commonly observed in elderly patients. Mortalin, a novel member of hsp 70 family of proteins, was initially identified by virtue of its association with a cellular mortal phenotype. Subsequently, normal cells and the ones with an immortal phenotype have been found to have differential subcellular localization of this protein. Antiproliferative activity of this protein in normal cells and the deregulation of expression in transformed cells is observed which suggests the association of mortalin in pathways that determine cellular divisional phenotype.
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PMID:Expression of endothelin, fibronectin, and mortalin as aging and mortality markers. 908 6

While a number of factors may initiate structural alterations within the cardiovascular system in response to hypertension, there are obligate cellular signaling mechanisms, such as the polyamines, through which they must operate. This study examined the effects of polyamine synthesis inhibition using eflornithine, a suicide inhibitor of ornithine decarboxylase on blood pressure, compensatory remodeling of the cardiovascular system, and cardiac and aortic polyamine contents using an aortic coarctation model in rats. Eflornithine treatment failed to reduce carotid arterial blood pressure and actually significantly elevated vascular pressure above and below the coarctation site by 14 days of hypertension. Eflornithine only transiently reduced aortic polyamine content of hypertensive rats while this agent reduced coarctation-induced aortic medial wall thickening and the synthesis/deposition of fibronectin and laminin in the hypertensive aorta. Increases in left ventricular mass and polyamine content were concomitantly reduced in hypertensive rats administered eflornithine. These results suggest that multiple polyamine regulatory pathways may maintain vascular polyamine content in response to aortic coarctation; however de novo polyamine synthesis is essential for select aspects of vascular remodeling, including matrix synthesis. Cardiac tissue, in contrast, may rely principally on de novo polyamine synthesis.
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PMID:Multiple polyamine regulatory pathways control compensatory cardiovascular hypertrophy in coarctation hypertension. 910 37

In recent years, a prodigious amount of information has been gathered regarding the relationship between vascular biology and the mechanisms underlying cardiovascular disease. Activation of elements of the reninangiotensin system (RAS) appear to play an important role in the development and progression of conditions such as hypertension, coronary artery disease, and heart failure. Indeed, converging lines of evidence indicate that angiotensin-converting enzyme (ACE) regulates a delicate balance among a multitude of factors responsible for vascular tone, cellular growth promotion and inhibition, and pro- and anti-inflammatory effects. Because angiotensin II inhibits fibronectin, stimulates expression of plasminogen activator inhibitors, and degrades bradykinin, thereby impairing production of nitric oxide, ACE and the RAS are also involved in thrombosis and fibrinolysis. The favorable effects of ACE inhibition on endothelial function and, potentially, on cardiovascular morbidity and mortality are believed to result not only from angiotensin II suppression but also its consequent bradykinin preservation and nitric oxide production.
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PMID:The integrated effects of angiotensin II. 912 15

A 15-year clinical follow-up is reported for a familial glomerulopathy characterized on light microscopy by the glomerular deposition of giant fibrillary deposits (Virchows Arch A Pathol Anat Histol 388:313-326, 1980). On electron microscopy, the deposits consist of randomly oriented fibrils (12 to 16 nm in width and 120 to 170 nm in length). These deposits show positive immunoreactivity for fibronectin. One hundred fifty-seven of 197 family members within five generations were investigated. The disease is characterized by the occurrence of albuminuria in the third to fourth decades of life and slow progression to end-stage renal disease over a period of 15 to 20 years with the occurrence of generalized distal tubular acidosis (renal tubular acidosis type IV), hypertension, and the nephrotic syndrome. The frequent occurrence of otherwise unexplained microalbuminuria in young individuals of generations IV and V could be indicative of incipient glomerular disease. In one affected male individual and in his unaffected sister, renal cell carcinoma was diagnosed, raising the possibility that this familial glomerulopathy might be associated with an increased risk to develop renal cell cancer by direct or indirect (associated genetic predisposition) mechanisms. The disease relapsed in one renal transplant, raising the possibility of the presence of a transferable factor that could be part of the deposited fibrillar material or, alternatively, interfere with the glomerular handling of the deposited material.
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PMID:Familial glomerulopathy with giant fibrillar (fibronectin-positive) deposits: 15-year follow-up in a large kindred. 915 3

To identify kidney biosynthetic abnormalities that may precede the onset of hypertension, we studied the expression of fibronectin (FN) and collagen IV (Coll IV) in young SHR (4 weeks of age) whose systolic blood pressure was normal and similar to that of age-matched control WKY rats. In isolated glomeruli the level of FN protein assessed by immunoblotting tended to be lower in the SHR than in the WKY rats. By Northern analysis the FN/actin mRNA ratio was significantly lower in glomeruli from SHR (0.56 +/- 0.47) than in glomeruli from WKY rats (2.0 +/- 0.8). These abnormalities were maintained in vitro since the expression of FN was significantly lower in SHR than in WKY cultured mesangial cells (FN/actin mRNA ratio = 0.84 +/- 0.46 vs. 1.9 +/- 0.7, P = 0.029). No differences in Coll IV mRNA or protein levels were observed in SHR glomeruli and mesangial cells when compared with WKY rats. The levels of aortic FN and Coll IV mRNAs were not different in SHR and WKY rats. In addition, mesangial cells from SHR showed a significantly higher growth rate than those from WKY. The biosynthetic and proliferative abnormalities observed in the SHR mesangial cells appear to reflect genetic characteristics, and could provide novel insights into cellular mechanisms linking the genetics of hypertension with predisposition to glomerular pathology.
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PMID:Mesangial cell abnormalities in spontaneously hypertensive rats before the onset of hypertension. 926 94

Our purpose was to evaluate fibronectin as a marker of endothelial cell injury, and as a test for predicting preeclampsia. A retrospective study was performed from November 1993 to March 1995. Results from 142 women were examined: 108 normal pregnant women and 34 pregnant women with evidence of preeclampsia. The plasma fibronectin concentration was significantly higher in pre-eclamptic gravidas (620 +/- 210 mg/l) than in normotensive gravidae women (390 +/- 130 mg/l). A fibronectin concentration lower than 400 mg/l predicted the non-development of a hypertension with a negative predictive value of 96%. The present findings suggest that fibronectin is rather an exclusion parameter than predictive test for hypertension disorders of pregnancy.
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PMID:Plasma fibronectin: predictive factor in gestational hypertension? 930 65

The preeclampsia-eclampsia syndrome is a vasospastic disorder and probably has a placental origin. Once the hypertensive syndrome is established the uteroplacental blood flow is reduced as well as the intervillous blood flow. Since 18-24 weeks of gestation and before the symptoms of preeclampsia become overt, changes in placental flow velocity can be detected with Doppler technics. The placental theories for the etiology of preeclampsia are focused on the hypoxic effect in the trophoblastic tissue of second trimester. The placental ischemic changes are evident and seen in the uteroplacental bed. They are interrelated with the stages of trophoblastic invasion of the spiral arteries during the 14 and 20 weeks. When the trophoblastic invasion is over, the spiral arteries become a high resistance system. The defect observed in preeclampsia is the lack of invasion of the trophoblast to the maternal arteries. The diminished placental perfusion probably creates endothelial damage. This damage has several effects: decreased prostaglandin production, activated coagulation cascade, stimulated fibrin aggregation, and increased vascular permeability. The ideal laboratory test for preeclampsia shall predict the onset of this entity. Recent findings seem promising. The fibronectin concentration increases 2-3 wks. prior to the clinical manifestation of preeclampsia. Severe hypertension shows an abnormal decrease in fibronectin levels. Hypocalciuria has been described as an early predictor in the development of preeclampsia. Other agents undergoing extensive evaluation as predictors are: uric acid, b-thromboglobin, prolactin and atrial natriuretic peptide. Recently high levels of b-HCG (human corionic gonadotrophin) have been linked to a lack of trophoblastic invasion during the second trimester, therefore this is a potential marker for those patients that will eventually develop preeclampsia.
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PMID:[Observations on pe-eclampsia-eclampsia and the advances in the evolution of some laboratory tests]. 931 19

Aging and hypertension are known to be closely related with the pathogenesis and development of glomerulosclerosis. In this study, we examined the time course changes in the glomerulus associated with salt-induced hypertension using the inbred Dahl salt-sensitive rats. For this purpose, 5-week-old Dahl salt-sensitive rats (n=36) were fed either 4% NaCl diet (n=18) or 0.3% NaCl diet (n=18) up to 17 weeks of age. The high salt diet caused a dramatic increase in systolic blood pressure and also a dramatic renal hypertrophy as shown by a significant increase in the kidney weight. Histological examination revealed an age-dependent progression of glomerulosclerosis as documented by a quantitative scoring. This age-dependent progression was further accelerated by the co-existence of salt-induced hypertension in the high salt diet group. Northern blot analysis revealed an increase in the steady state mRNA levels of fibronectin, an important component of mesangial matrices, in the renal cortex, but not in the renal medulla, only in salt-loaded Dahl salt-sensitive rats. These findings indicate that salt-induced hypertension accelerates the age-dependent progression of glomerulosclerosis in Dahl salt-sensitive rats, and fibronectin may play a role in the pathogenesis, development, and progression of glomerulosclerosis associated with salt-induced hypertension.
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PMID:Progression of glomerulosclerosis, renal hypertrophy, and an increased expression of fibronectin in the renal cortex associated with aging and salt-induced hypertension in Dahl salt-sensitive rats. 935 64

Autosomal dominant polycystic kidney disease (ADPKD) progresses to end-stage renal insufficiency before the age of 73 in approximately 48% of affected individuals. Why the disease, characterized by innumerable cysts arising in proximal and distal tubules, eliminates functioning non-cystic parenchyma in some patients and spares other is a mystery. The cysts initiate in early childhood in fewer than 1% of renal tubules as a consequence of the focal expression of mutated DNA. Tubule cells proliferate, causing segmental dilation, in association with the abnormal deposition of extracellular matrix proteins. Most of the cysts separate from the parent tubules and fill with fluid by cAMP-mediated chloride secretion. Risk factors associated with accelerated loss of renal function include: genotype (PKD Type 1 progresses more rapidly than PKD Type 2); gender (males progress more rapidly than females); race (black patients progress more rapidly than whites); hypertension; proteinuria. The relation between kidney size and progression to renal failure is debated. Progressive PKD is associated with the cellular expression of proto-oncogenes (fos, myc, ras, erb), growth factors (EGF, HGF, acid and basic FGF), chemokines (MCP-1. osteopontin), metalloproteinases, and apoptotic markers, and the interstitial accumulation of Types I and IV collagen, laminin, fibronectin, macrophages and fibroblasts, the magnitudes of which increase with age. Cyst activating factor (CAF), a neutral lipid identified in cyst fluid that stimulates fluid secretion and proliferation of renal epithelial cells and monocyte chemotaxis, has recently been identified as a potential progression factor. In those patients destined to develop renal failure there is loss of non-cystic parenchyma in association with mass replacement by fluid-filled cysts in a network of interstitial fibrosis. The decline in renal function is probably the consequence of processes leading to interstitial fibrosis, as in other nephropathies, rather than due to simple mechanical displacement of parenchyma by cysts.
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PMID:Mechanisms of progression in autosomal dominant polycystic kidney disease. 940 32


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