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)

We report the case of a 52-yr-old man with a mass in the area of the left adrenal. The clinical features, MIBG uptake, and elevated urinary dopamine levels suggested the diagnosis of pheochromocytoma. He presented with unstable hypertension, tachycardia, weight loss, and the "inflammatory syndrome" (fever, leukocytosis, and high sedimentation rate). Clinical findings, preoperative radiographic (sonography, CT scan, [131I]MIBG scintigraphy), and endocrine evaluations (elevated 24-h urinary dopamine) were suggestive of a dopamine-secreting adrenal tumor. The mass was resected and on histologic examination showed the characteristic features of a malignant fibrous histiocytoma (MFH). The tumor cells were immunopositive for neuron-specific enolase (NSE), vimentin, CD-68, S-100, desmin, and immunonegative for chromogranin A, synaptophysin, neurofilament protein, and low-molecular-weight keratin, indicating that this tumor was not able to synthesize catecholamines. The prolonged retention of the tracer (MIBG) was interpreted as a consequence of obstructive hydronephrosis, while elevated urinary dopamine levels were assumed to be due to compression of the renal vessels by the large retroperitoneal mass.
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PMID:Retroperitoneal malignant fibrous histiocytoma mimicking pheochromocytoma. 1524 9

We have previously demonstrated that restricting intrauterine food by 50% in 3-mo-old rats produced lower nephron numbers and early-onset hypertension, the latter being normalized by L-arginine administration. In 18-mo-old rats, such restriction increased glomerulosclerosis. In this study, we expanded our investigation, evaluating functional, morphologic, and immunohistochemical parameters in intrauterine-food-restricted 18-mo-old rats, either receiving L-arginine (RA18) or not (R18). Age-matched, non-food-restricted controls were assigned to similar groups with L-arginine (CA18) and without (C18). After weaning, L-arginine was given daily for 17 mo. No functional or morphologic changes were observed in C18 rats. The R18 rats developed early-onset hypertension, which persisted throughout the observation period, as well as significant proteinuria from 12 mo on. In RA18 rats, L-arginine decreased both blood pressure levels and proteinuria, and glomerular diameter was significantly smaller than in R18 rats (115.63 +/- 2.2 versus 134.8 +/- 1.0 mum, p < 0.05). However, in RA18 rats, glomerular filtration rate remained depressed. Although L-arginine prevented glomerulosclerosis (R18 = 14%, RA18 = 4%; p < 0.05), glomerular expression of fibronectin and desmin was still greater in RA18 rats than in controls. Our data show that, although L-arginine prevented hypertension and proteinuria, glomerular injury still occurred, suggesting that intrauterine food restriction may be one of the leading causes of impaired renal function in adult life.
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PMID:Effects of intrauterine food restriction and long-term dietary supplementation with L-arginine on age-related changes in renal function and structure of rats. 1577 22

Recent clinical studies implicate proteinuria as a key prognostic factor for renal and cardiovascular complications in hypertensives. The pathogenesis of proteinuria in hypertension is, however, poorly elucidated. Podocytes constitute the final filtration barrier in the glomerulus, and their dysfunction may play a pivotal role in proteinuria. In the present study, we examined the involvement of podocyte injury in Dahl salt-hypertensive rats, an animal model prone to hypertensive glomerulosclerosis, and explored the effects of inhibition of aldosterone. Four-week-old Dahl salt-resistant and salt-sensitive rats were fed a 0.3% or 8.0% NaCl diet. Some salt-loaded Dahl salt-sensitive rats were treated with a selective aldosterone blocker eplerenone (1.25 mg/g diet) or hydralazine (0.5 mmol/L). After 6 weeks, salt-loaded Dahl salt-sensitive rats developed severe hypertension, proteinuria, and glomerulosclerosis. Immunostaining for nephrin, a constituent of slit diaphragm, was attenuated, whereas expressions of damaged podocyte markers desmin and B7-1 were upregulated in the glomeruli of salt-loaded Dahl salt-sensitive rats. Electron microscopic analysis revealed podocyte foot process effacement. Podocytes were already impaired at as early as 2 weeks of salt loading in Dahl salt-sensitive rats, when proteinuria was modestly increased. Both eplerenone and hydralazine partially reduced systemic blood pressure as measured by indirect and direct methods in salt-loaded Dahl salt-sensitive rats, but only eplerenone dramatically improved podocyte damage and retarded the progression of proteinuria and glomerulosclerosis. Our findings suggest that podocyte injury underlies the glomerulopathy of Dahl salt-hypertensive rats and that inhibition of aldosterone by eplerenone is protective against podocyte damage, proteinuria, and glomerulosclerosis in this hypertensive model.
Hypertension 2006 Jun
PMID:Podocyte injury underlies the glomerulopathy of Dahl salt-hypertensive rats and is reversed by aldosterone blocker. 1663 93

Metabolic syndrome is an important risk factor for proteinuria and chronic kidney disease independent of diabetes and hypertension; however, the underlying mechanisms have not been elucidated. Aldosterone is implicated in target organ injury of obesity-related disorders. This study investigated the role of aldosterone in the early nephropathy of 17-wk-old SHR/NDmcr-cp, a rat model of metabolic syndrome. Proteinuria was prominent in SHR/NDmcr-cp compared with nonobese SHR, which was accompanied by podocyte injury as evidenced by foot process effacement, induction of desmin and attenuation of nephrin. Serum aldosterone level, renal and glomerular expressions of aldosterone effector kinase Sgk1, and oxidative stress markers all were elevated in SHR/NDmcr-cp. Mineralocorticoid receptors were expressed in glomerular podocytes. Eplerenone, a selective aldosterone blocker, effectively improved podocyte damage, proteinuria, Sgk1, and oxidant stress. An antioxidant tempol also alleviated podocyte impairment and proteinuria, along with inhibition of Sgk1. As for the mechanisms of aldosterone excess, visceral adipocytes that were isolated from SHR/NDmcr-cp secreted substances that stimulate aldosterone production in adrenocortical cells. The aldosterone-releasing activity of adipocytes was not inhibited by candesartan. Adipocytes from nonobese SHR did not show such activity. In conclusion, SHR/NDmcr-cp exhibit enhanced aldosterone signaling, podocyte injury, and proteinuria, which are ameliorated by eplerenone or tempol. The data also suggest that adipocyte-derived factors other than angiotensin II might contribute to the aldosterone excess of this model.
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PMID:Enhanced aldosterone signaling in the early nephropathy of rats with metabolic syndrome: possible contribution of fat-derived factors. 1708 36

We report a 40-year-old lady who presented with severe headaches, persistent microscopic haematuria and hypertension requiring anti-hypertensive medication. Investigations for secondary hypertension were all normal except for a CT scan. This indicated a complex cystic lesion, measuring 2.4 x 5 x 10 cms , arising from the right kidney. She underwent an open right partial nephrectomy. The patient made an un-eventful postoperative recovery and her blood pressure returned to normal. The mass had a smooth outer surface and the cut surface showed firm whitish tissue with a few small cysts. Microscopy showed a bland spindle cell lesion staining positively for SMA, desmin, caldesmon, focally for HMB45 amd very focally for S100. The mass was reported as a Perivascular Epitheloid Cell (PEC) lesion (PEComa) arising from the renal capsule. Perivascular Epitheloid Cell tumor (PEComa), a recently defined tumor, is extremely rare. The lesion presents a distinct muscular immunophenotype (actin+, desmin+), with co-expression of the melanogenesis marker (HMB45). This combined immunophenotype is a characteristic feature of the Perivascular Epitheloid Cell (PEC) lesions. PEComa's are usually benign, but cases have been reported in the literature which has an unfavourable outcome with metastatic dissemination. We report this case because of its rarity and also Renal Capsular PEComa should be considered as a rare cause of renal hypertension, which can be surgically cured.
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PMID:Renal capsular PEComa--a rare cause of surgically correctable renal hypertension. 1731 50

We report a rare case of sertoliform endometrioid carcinoma of the endometrium in a 71-year-old African American woman who presented with postmenopausal bleeding. Her medical condition was remarkable for hypertension, diabetes, and obesity. She underwent total hysterectomy, right salpingo-oophorectomy and lymph node sampling. The endometrium was occupied by a 4.5-cm solid polypoid tumor, which grossly invaded into the myometrium. Microscopically, the tumor consisted of small hollow tubules, anastomosing cords and trabeculae, and tightly packed nests. Microglandular areas mimicking adult granulosa cell tumors were also present. But true Call-Exner bodies were absent. Component of typical endometrioid carcinoma was noted only focally. The uninvolved endometrium demonstrated atypical complex hyperplasia. The tumor cells were diffusely immunoreactive for epithelial membrane antigen, estrogen receptor, and progesterone receptor (PR), and focally for vimentin. The tumor cells were also diffusely positive for inhibin alpha and CD99. Immunostains for other sex cord markers (calretinin, WT-1, and Melan-A) were also positive in approximately 30% to 40% of the tumor cells. Immunostains for CD10, smooth muscle actin, desmin, or HHF35 were negative. Two ovarian sertoliform endometrioid carcinomas from our archived tissue were, however, immunoreactive for epithelial membrane antigen but negative for inhibin alpha. Despite the prominent sertoliform features, both histologically and immunohistochemically, the tumor was of a high-grade endometrial carcinoma and will likely behave as such. As of today, dual differentiation of epithelium and sex cord by immunohistochemical staining has not been demonstrated in sertoliform endometrioid carcinomas of either endometrial or ovarian origin. Our case is the first documentation of such example and suggests that endometrial carcinoma can undergo true sex cord differentiation.
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PMID:Sertoliform endometrioid carcinoma of the endometrium with dual immunophenotypes for epithelial membrane antigen and inhibin alpha: case report and literature review. 1758 14

Obesity and hypertension have been identified as cardiovascular risk factors that contribute to the progression of end-stage renal disease. To examine the mechanisms by which a high-fat diet and hypertension contribute to endothelial dysfunction and renal injury, 8-week-old male spontaneously hypertensive rats and Wistar rats were fed a high-fat (36% fat) or a normal-fat (7% fat) diet for 10 weeks. The high-fat diet increased body weight in Wistar and hypertensive rats by 25 and 31 g, respectively. Systolic blood pressure was higher in the hypertensive rats compared with Wistar rats; however, blood pressure was unaltered by the high-fat diet. Afferent arteriole response to acetylcholine was impaired in the high-fat groups after just 3 weeks. Renal macrophage infiltration was increased in the hypertensive high-fat group compared with others, and monocyte chemoattractant protein-1 excretion was increased in both of the high-fat-fed groups. Renal PCR arrays displayed significant increases in 2 inflammatory genes in hypertensive rats fed a normal diet, 1 gene was increased in high-fat-fed Wistar rats, whereas 12 genes were increased in high-fat-fed hypertensive rats. Urinary albumin excretion was increased in the hypertensive rats compared with the Wistar rats, which was further exacerbated by the high-fat diet. Glomerular nephrin expression was reduced and desmin was increased by the high-fat diet in the hypertensive rats. Our results indicate that endothelial dysfunction precedes renal injury in normotensive and spontaneously hypertensive rats fed a high-fat diet, and hypertension with obesity induces a powerful inflammatory response and disruption of the renal filtration barrier.
Hypertension 2008 Feb
PMID:Endothelial dysfunction and the development of renal injury in spontaneously hypertensive rats fed a high-fat diet. 1815 49

Our previous studies in heterozygous Ren-2 transgenic rats (TGR) have shown that early treatment with selective endothelin (ET)(A) receptor blockade is superior to nonselective ET(A/B) receptor blockade. The aim of this study was to evaluate the role of the ET system in male heterozygous TGR with established hypertension (late-onset treatment). TGR and control Hannover Sprague-Dawley (HanSD) rats were fed a high-salt diet and were treated concomitantly with the nonselective ET(A/B) receptor blocker bosentan or the selective ET(A) receptor blocker atrasentan from day 52 of age on. Survival rate was partly increased by bosentan and fully normalized with atrasentan. Bosentan transiently decreased blood pressure (BP), whereas atrasentan significantly reduced BP as early as one week after the start of the treatment. This effect persisted for the whole experimental period. Atrasentan also substantially reduced cardiac hypertrophy, proteinuria, glomerulosclerosis and left ventricle ET-1 content. Bosentan improved and atrasentan almost restored podocyte architecture and reversed changes in podocyte phenotype represented by the expression of CD 10, desmin and vimentin. Our results demonstrate that selective ET(A) receptor blockade has more favorable effects than nonselective ET(A/B) receptor blockade and, unlike observed in homozygous TGR, ET(A) receptor blockade has similar effects in heterozygous rats with established hypertension as in young animals with developing hypertension.
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PMID:Late-onset endothelin receptor blockade in hypertensive heterozygous REN-2 transgenic rats. 1837 20

Pheochromocytomas are widely believed to induce cardiomyopathy via hypersecretion of catecholamines, including norepinephrine (NE). NE can have direct cardiomyocyte toxicity and/or can stimulate myocardial remodeling secondary to the induction of hypertension. Yet, the development of cardiomyopathy is not entirely related to catecholamine dose or the extent of hypertension. To explore these effects, we engineered a polymeric encapsulation system to control PC12 cell kinetics and NE release in vitro and in vivo. Primary neonatal rat cardiomyocytes incubated with pheochromocytoma-conditioned media exhibited greater cytoskeletal changes than myocytes cultured with identical doses of NE alone, including more profound dose-dependent decreases in desmin, beta-tubulin, and vinculin and upregulation of dystrophin. Cardiomyocyte contractility was 29 +/- 6% greater at given levels of NE release. Agarose-encapsulated PC12 cells retain cell viability and structural integrity in vivo. These implants induce a 30% greater degree of cardiac enlargement as compared to pumps releasing equivalent doses of NE. Protein level alterations observed in vitro were mirrored in vivo after implantation of encapsulated cells or NE pumps for 28 days. Together, these data suggest that pheochromocytoma-induced cardiomyopathy is not solely a catecholamine-mediated event; rather, the pathogenesis of this dilated cardiomyopathy appears to be dependent upon secondary factors unexamined to date.
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PMID:Encapsulated pheochromocytoma cells secrete potent noncatecholamine factors. 1912 41

Poor fetal growth is linked with long-term detrimental effects on health in late life. We have previously shown that maternal protein restriction leads to hypertension and a reduced number of glomeruli in adult offspring. The aim of this study was to investigate the influence of a postnatal high-protein (HP) diet on renal development and renal function in rats subjected to a low-protein (LP) diet in fetal life. Sprague-Dawley rats were fed an LP diet throughout pregnancy. Male pups were given either a normal-protein (NP) diet (LP/NP) or HP diet (LP/HP), and normal male pups as control (NP/NP). At 12 wk, LP/HP offspring displayed no increase in glomerular number but showed elevated blood pressure and proteinuria compared with the LP/NP group. There was minimal fusion of foot processes in LP/NP rats compared with a moderate fusion of foot processes and hyperplasia of mesangial cells in LP/HP rats. Renal desmin mRNA levels were elevated in both LP/NP and LP/HP groups but more significantly in the LP/HP group. This study suggests that postnatal HP diet amplifies the renal damage induced by fetal under-nutrition. Podocyte injury may be one of the mechanisms by which fetal protein restriction leads to proteinuria.
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PMID:Effect of postnatal high-protein diet on kidney function of rats exposed to intrauterine protein restriction. 2045 15


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