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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case report of a 55-year-old woman with an incidentally diagnosed urinary paraganglioma of the bladder is presented. The patient had no irritative voiding symptoms, hematuria or hypertension. She was diagnosed to have an immobile solid mass on the left side neighboring the lower segment of the uterus. Transvaginal ultrasonography revealed a well-limited ovoid mass with solid and cystic areas adjacent to the urinary bladder and the uterus. Tumor markers were within normal range. Laparoscopy was performed for the treatment of the mass and complete excision of the cyst was accomplished. Frozen section was performed revealing a benign cystic structure but the identification of the origin was left to definitive histopathological examination which showed paraganglioma of the bladder. Immunohistochemically, the tumor cells were strongly positive for chromogranin A and synaptophysin and there was focal positiveness for neuron specific enolase although vimentin and cytokeratin were negative.
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PMID:Laparoscopic resection of urinary bladder paraganglioma: a case report. 1655 85

Family studies have suggested a genetic contribution to variation in blood pressure, but the genes responsible have thus far eluded identification. The use of intermediate phenotypes associated with hypertension, such as chromogranin plasma concentrations, may assist the discovery of hypertension-predisposing loci. We measured the concentrations of four chromogranin A (CHGA) and B (CHGB) peptides in 742 individuals from 235 nuclear families. The CHGA- and CHGB-derived peptides displayed significant heritability and revealed significant genetic correlations, most strikingly observed between CHGA(361-372) (catestatin) and CHGB(439-451). A 5-cM microsatellite genome scan revealed significant and suggestive evidence for linkage on several chromosomes for three of the peptides. Subsequent bivariate linkage analysis for peptides CHGA(361-372) and CHGB(439-451), which showed evidence for convergent linkage peaks on chromosomes 2, 7, and 13, resulted in increased evidence for linkage to these regions, suggesting pleiotropic effects of these three loci on multiple chromogranin traits. Because CHGA itself is on chromosome 14q32, and CHGB itself is on chromosome 20pter-p12, the pleiotropic regions on chromosomes 2, 7, and 13 must represent trans-acting quantitative trait loci coordinately affecting CHGA/CHGB biosynthesis and/or exocytotic secretion, likely by regulating efferent sympathetic outflow, a conclusion consistent with the in vitro studies presented here of the dual control of both exocytosis and transcription of these peptides by secretory stimuli in chromaffin cells. The results suggest a new approach to heritable autonomic control of circulation and the genetic basis of cardiovascular diseases such as systemic hypertension.
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PMID:Pleiotropic effects of novel trans-acting loci influencing human sympathochromaffin secretion. 1655 46

A 60-year-old male patient with hypertension was referred to our hospital because of insufficient blood pressure control (190/98 mmHg) and to rule out secondary hypertension. A computed tomography scan revealed no adrenal tumor but a large liver mass (5 x 5 cm), and magnetic resonance imaging showed a high signal intensity lesion on the T2-weighted image. Twenty-four hour urinary excretion of catecholamine metabolites was markedly increased, although a 123I-metaiodobenzyl guanidine (MIBG) scintigram failed to show accumulation in the hepatic mass, and no difference was noted between the catecholamine concentration in the tumor-drainage vein and that obtained from the vein draining from the non-tumor area. Liver biopsy did show features compatible with pheochromocytoma (i.e., chromogranin A-positive cells). Transcatheter arterial embolization of the liver tumor was conducted and resulted in a marked (50%) decrease in the 24-h urine normetanephrine excretion. Several metastatic foci were noted in the spinal bone and transcatheter arterial embolization (TAE) was also conducted with successful results. Thus, we experienced a case of primary malignant hepatic pheochromocytoma with negative 123I-MIBG scanning.
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PMID:Primary malignant hepatic pheochromocytoma with negative adrenal scintigraphy. 1704 68

Albumin excretion marks early glomerular injury in hypertension. This study investigated heritability of albumin excretion in twin pairs and its genetic determination by adrenergic pathway polymorphism. Genetic associations used single nucleotide polymorphisms at adrenergic pathway loci spanning catecholamine biosynthesis, storage, catabolism, receptor action, and postreceptor signal transduction. We studied 134 single nucleotide polymorphisms at 46 loci for a total of >51,000 genotypes. Albumin excretion heritability was 45.2+/-7.4% (P=2x10(-7)), and the phenotype aggregated significantly with adrenergic, renal, metabolic, and hemodynamic traits. In the adrenergic system, excretions of both norepinephrine and epinephrine correlated with albumin. In the kidney, albumin excretion correlated with glomerular and tubular traits (Na(+) and K(+) excretion; fractional excretion of Na(+) and Li(+)). Albumin excretion shared genetic determination (genetic covariance) with epinephrine excretion, and environmental determination with glomerular filtration rate and electrolyte intake/excretion. Albumin excretion associated with polymorphisms at multiple points in the adrenergic pathway: catecholamine biosynthesis (tyrosine hydroxylase), catabolism (monoamine oxidase A), storage/release (chromogranin A), receptor target (dopamine D1 receptor), and postreceptor signal transduction (sorting nexin 13 and rho kinase). Epistasis (gene-by-gene interaction) occurred between alleles at rho kinase, tyrosine hydroxylase, chromogranin A, and sorting nexin 13. Dopamine D1 receptor polymorphism showed pleiotropic effects on both albumin and dopamine excretion. These studies establish new roles for heredity and environment in albumin excretion. Urinary excretions of albumin and catecholamines are highly heritable, and their parallel suggests adrenergic mediation of early glomerular permeability alterations. Albumin excretion is influenced by multiple adrenergic pathway genes and is, thus, polygenic. Such functional links between adrenergic activity and glomerular injury suggest novel approaches to its prediction, prevention, diagnosis, and treatment.
Hypertension 2007 May
PMID:Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism. 1735 15

The plasma level of chromogranin A (CgA) is elevated in genetic hypertension. Conversely, the plasma level of the CgA peptide catestatin is diminished in individuals with established hypertension and those with a genetic risk of this disease. Resequencing of the human CHGA gene identified three naturally occurring variants of catestatin (Gly364Ser, Pro370Leu, and Arg374Gln) that exhibit different potencies in inhibiting catecholamine secretion. Here, we have examined whether there is any differential processing of the three CHGA variants to catestatin by the endoproteolytic enzyme plasmin. Plasmin digestion of the purified CgA proteins generated a stable biologically active 14-amino acid peptide (human CgA(360-373)) from the wild-type, Gly364Ser, and Arg374Gln proteins despite the disruption of the dibasic site (Arg(373)Arg(374)) in the Arg374Gln variant. Unexpectedly, the action of plasmin in generating the catestatin peptide from the Pro370Leu protein was less efficient. The efficiency of cleavage at the dibasic Arg(373) downward arrowArg(374) site in synthetic human CgA(360-380) was 3- to 4-fold less in Pro370Leu CgA, compared with the wild type. Circular dichroism of the synthetic CgA(352-372) suggested a difference in the amount of alpha-helix and beta-sheet between the wild-type and Pro370Leu CgA peptides. Because the Pro(370) residue is in the P4 position, the local secondary structure in the vicinity of the cleavage site may enforce the specificity or accessibility to plasmin. The less efficient proteolytic processing of the Pro370Leu protein by plasmin, coupled with the strong association of this variant with ethnicity, suggests that the Pro370Leu CHGA gene variant may contribute to the differential prevalence of cardiovascular disease across ethnic groups.
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PMID:Proteolytic cleavage of human chromogranin a containing naturally occurring catestatin variants: differential processing at catestatin region by plasmin. 1799 25

Chromogranin A is released together with epinephrine and norepinephrine from catecholaminergic cells. Specific endopeptidases cleave chromogranin A into biologically active peptide fragments, including catestatin, which inhibits catecholamine release. Previous studies have suggested that a deficit in this sympathetic "braking" system might be an early event in the pathogenesis of human hypertension. Whether chromogranin A (CHGA) polymorphisms predict end-organ complications of hypertension, such as end-stage renal disease, is unknown. Among blacks, we studied common genetic variants spanning the CHGA locus in 2 independent case-control studies of hypertensive ESRD. Two haplotypes were significantly more frequent among subjects with hypertensive ESRD: 1) in the promoter (5') region, G-462A-->T-415C-->C-89A, haplotype ATC (adjusted odds ratio = 2.65; P = 0.037), and 2) at the 3'-end, C11825T (3'-UTR, C+87T)-->G12602C, haplotype TC (adjusted odds ratio = 2.73, P = 0.0196). Circulating levels of catestatin were lower among those with hypertensive ESRD than controls, an unexpected finding given that peptide levels are usually elevated in ESRD because of reduced renal elimination. We found that the 3'-UTR + 87T variant decreased reporter gene expression, providing a possible mechanistic explanation for diminished catestatin. In summary, common variants in chromogranin A associate with the risk of hypertensive ESRD in blacks.
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PMID:Chromogranin A polymorphisms are associated with hypertensive renal disease. 1827 38

Circulating levels of catestatin (Cts; human chromogranin A352-372) decrease in the plasma of patients with essential hypertension. Genetic ablation of the chromogranin A (Chga) gene in mice increases blood pressure and pretreatment of Chga-null mice with Cts prevents blood pressure elevation, indicating a direct role of Cts in preventing hypertension. This notable vasoreactivity prompted us to test the direct cardiovascular effects and mechanisms of action of wild-type (WT) Cts and naturally occurring human variants (G364S-Cts and P370L-Cts) on myocardial and coronary functions. The direct cardiovascular actions of WT-Cts and human variants were determined using the Langendorff-perfused rat heart. WT-Cts dose-dependently increased heart rate and coronary pressure and decreased left ventricular pressure, rate pressure product and both positive and negative LVdP/dt. WT-Cts not only inhibited phospholamban phosphorylation, but also the inotropic and lusitropic effects of WT-Cts were abolished by chemical inhibition of beta2-adrenergic receptors, Gi/o protein, nitric oxide or cGMP, indicating involvement of beta2-adrenergic receptors-Gi/o protein-nitric oxide-cGMP signaling mechanisms. In contrast, G364S-Cts did not affect basal cardiac performance but abolished isoproterenol-induced positive inotropism and lusitropism. P370L-Cts decreased rate pressure product and inhibited only isoproterenol-induced positive inotropism and lusitropism by 70%. Cts also inhibited endothelin-1-induced positive inotropism and coronary constriction. Taken together, the cardioinhibitory influence exerted on basal mechanical performance and the counterregulatory action against beta-adrenergic and endothelin-1 stimulations point to Cts as a novel cardiac modulator, able to protect the heart against excessive sympathochromaffin overactivation, e.g. hypertensive cardiomyopathy.
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PMID:The antihypertensive chromogranin a peptide catestatin acts as a novel endocrine/paracrine modulator of cardiac inotropism and lusitropism. 1880 48

Catestatin is a 21-amino acid residue, cationic and hydrophobic peptide that is formed endogenously by proteolytic cleavage of its precursor chromogranin A, a major protein co-stored and co-released with catecholamines from the storage vesicles in adrenal chromaffin cells and adrenergic neurons. This peptide exhibits potent catecholamine release-inhibitory activity by acting on the neuronal nicotinic acetylcholine receptor. It also stimulates histamine release from mast cells via heterotrimeric G-proteins in a receptor-independent manner. Plasma levels of catestatin are diminished not only in hypertensive patients but also in their still-normotensive offspring, indicating its role in the pathogenesis of hypertension. Consistently, exogenous catestatin rescues hypertension in chromogranin A knockout mice and diminishes blood pressure responses to activation of sympathetic outflow in rats. These hypotensive actions of catestatin may be caused directly by autocrine inhibition of catecholamine release from the sympathoadrenal system and indirectly by paracrine stimulation of the potent vasodilator histamine release from mast cells. Recently, three human variants of catestatin displaying differential potencies for inhibition of catecholamine secretion have been identified. One of these variants (Gly364Ser) causes increased baroreceptor sensitivity, increased cardiac parasympathetic activity, and decreased cardiac sympathetic activity, and it seems to alter the risk for hypertension. These cardiovascular effects may have resulted by action of this peptide in the baroreceptor centre of the nucleus tractus solitarius. Thus, accumulating evidence documents the endogenous peptide catestatin as a novel regulator of cardiac function and blood pressure.
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PMID:Catestatin is a novel endogenous peptide that regulates cardiac function and blood pressure. 1854 22

The authors report the case of a 46-year-old woman who presented with a 4 month history of paroxystic and recent hypertension accompagned by headaches, tachycardia and sweating. The patient had decreased appetite with epigastric discomfort and abdominal distension. Physical examination was initially normal with mainly normal tension and no abdominal or lombar mass in palpation. While hospitalised, she developed paroxystic crisis of flush, headaches and hypertension of 190/100 mmHg. Biological findings revealed hypokaliemia and normal kaliuria on 3 day samples, with normal glycaemia and normal creatininaemia. Hormonal investigation revealed elevated metanephrines (3 mg/24 hours). Magnetic resonance imaging showed an 11 cm x 8.5 cm retroperitoneal mass with an enhanced signal in T2, a hypotrophic non-functional left kidney and no adrenal adenoma. Clinical and hormonal features suggested a diagnosis of pheochromocytoma. After preoperative medication, open excision, including left radical nephrectomy and adrenalectomy, normalized the catecholamine urinary level, resolved hypokalemia, and improved hypertension. Pathologic examination revealed a well-differentiated liposarcoma, without any pheochromocytoma component, and left adrenal hyperplasia. The tumour cells were immunonegative for chromogranin A. No metastatic lesion was identified by thoraco-abdominal computed tomography.
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PMID:Retroperitonial liposarcoma mimicking pheochromocytoma. 1947 89

Pheochromocytomas are uncommon neoplasms of the adrenal medulla that are most frequently reported in rats and select mouse strains. In many cases, especially those in man, pheochromocytoma is associated with familial tumor syndromes, because of inherited mutations in a variety of proto-oncogenes and tumor suppressor genes. Nonhuman primates are valuable animal models for a variety of human diseases because of their similar anatomy and physiology; however, cases of pheochromocytomas have only rarely been reported in nonhuman primates. Herein, we characterize the gross, histologic, and immunohistochemical features of pheochromocytoma in 6 cotton-top tamarins (Saguinus oedipus). Pheochromocytomas represented 6 of 114 of the total causes of death in the studied population (5.3%) and corresponded to 16% of the total number of neoplasms. The average age of affected animals was 17.9 years. On histologic examination, all cases were defined by tight bundles, nests, and cords of neoplastic chromaffin cells. All cases had concurrent myocardial degeneration and fibrosis of varying severity and chronicity. Three of the cases (50%) also had hyalinization and medial thickening of coronary arteries consistent with hypertension. On immunohistochemical examination, 6 of 6 of the cases (100%) stained positively for chromogranin A, synaptophysin, N-CAM (or CD56), and protein gene product 9.5. None of the cases stained for glial fibrillary acidic protein. Pedigree analysis revealed inter-relatedness in 4 of 6 animals, with progenitor animals also affected with pheochromocytomas. The tumors in this population illustrate comparable histologic and immunohistochemical staining patterns with cases in other laboratory animals and humans, and, therefore, may indicate common underlying genetic alterations that precipitate tumor development.
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PMID:Histologic and immunohistochemical characterization of pheochromocytoma in 6 cotton-top tamarins (Saguinus oedipus). 1960 96


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