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)

Factitious pheochromocytoma usually occurs in patients surreptitiously ingesting adrenergic medications. We encountered a case of factitious pheochromocytoma where in the subject mimicked hemodynamic (profound hypertension) and biochemical (plasma catecholamine elevation) manifestations of the illness by consciously altering autonomic function with Valsalva maneuver. Clues to this presentation included visible performance of Valsalva maneuver, marked disparity between blood pressures recorded in the presence and absence of the subject's knowledge, normal urinary catecholamine and metabolite excretion, and normal plasma chromogranin A. We reproduced, in part, the hemodynamic and biochemical manifestations of this presentation with Valsalva maneuver in healthy subjects.
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PMID:Factitious pheochromocytoma: novel mimickry by Valsalva maneuver and clues to diagnosis. 766 52

Although measurement of chromogranin A in the bloodstream is of value in sympathoadrenal investigations, little is systematically known about chromogranin A in cerebrospinal fluid, despite substantial knowledge about its occurrence and distribution in brain. We therefore applied a homologous human chromogranin A radioimmunoassay to cerebrospinal fluid, in order to evaluate the properties and stability of cerebrospinal fluid chomogranin A, as well as its relationship to central noradrenergic neuronal activity, to peripheral (plasma) chromogranin A, and to disease states such as hypertension, renal failure and Parkinsonism. Authentic, physically stable chromogranin A immunoreactivity was found in cerebrospinal fluid (at 37-146 ng/ml; mean, 87.0 +/- 6.0 ng/ml in healthy subjects), and several lines of evidence (including 3.39 +/- 0.27-fold higher chromogranin A in cerebrospinal fluid than in plasma) indicated that it originated from a local central nervous system source, rather than the periphery. Cerebrospinal fluid chromogranin A values were not influenced by administration of effective antihypertensive doses of clonidine or propranolol, and were not related to the cerebrospinal fluid concentrations of norepinephrine, methoxyhydroxyphenylglycol, or dopamine-beta-hydroxylase; thus, cerebrospinal fluid chromogranin A was not closely linked to biochemical or pharmacologic indices of central noradrenergic neuronal activity. Cerebrospinal fluid chromogranin A was not changed (P > 0.1) in essential hypertension (84.2 +/- 14.0 ng/ml) or renal failure (72.2 +/- 13.4 ng/ml), despite a marked (7.1-fold; P < 0.001) increase in plasma chromogranin A in renal failure, and a modest (1.5-fold; P = 0.004) increase in plasma chromogranin A in essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chromogranin A immunoreactivity in human cerebrospinal fluid: properties, relationship to noradrenergic neuronal activity, and variation in neurologic disease. 790 34

We assessed the clinical utility of serum chromogranin A (CgA) alone and in combination with plasma catecholamines in the diagnosis of pheochromocytoma in patients with mild to moderate renal impairment. The study population consisted of 44 normal subjects, 50 subjects with proven pheochromocytoma, and 82 subjects with hypertension (60 primary and 22 secondary) suspected but not proven to have the disease. In this highly selected group with high disease prevalence (38%), the overall sensitivity, specificity, accuracy, and positive and negative predictive values of serum CgA in the diagnosis of pheochromocytoma were 86%, 74%, 79%, 67%, and 94%, respectively. However, in patients with creatinine clearance less than 1.33 mL/s (80 mL/min), these values dropped to 85%, 50%, 59%, 38%, and 90%, respectively. The combination of plasma catecholamines and CgA provided the best overall specificity (95%), accuracy (88%), and positive predictive value (91%). In patients with a creatinine clearance of more than 1.33 mL/s, the combination gave a specificity of 98%, an accuracy of 89%, and a positive predictive value of 97%. These results show that serum CgA has poor diagnostic specificity in the diagnosis of pheochromocytoma when renal function is impaired. Combining CgA with plasma catecholamines provides a lower sensitivity, but excellent specificity, accuracy, and positive predictive value.
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PMID:Diagnostic specificity of serum chromogranin-A for pheochromocytoma in patients with renal dysfunction. 817 70

Chromogranin A is an acidic protein, stored and released with catecholamines, and is overexpressed in genetic hypertension. In the human genome, its locus has previously been positioned on the long arm of Chromosome 14 in the 14q32 region. As a first step toward evaluating its potential linkage with hereditary hypertension, we determined its chromosomal position in mouse and rat. Chromogranin A was present as a single-copy gene in both mouse and rat. Analysis of the allele distribution in an interspecific mouse backcross by single-strand conformation polymorphism positioned the chromogranin A locus on Chromosome 12, between Igh-C and D12Pas1. Evaluation of a rat/mouse somatic cell hybrid panel indicated that chromogranin A is on rat Chromosome 6. In each case (mouse, rat, and human), chromogranin A is in a conserved region with nearby markers including the immunoglobulin heavy chain locus.
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PMID:Assignment of the chromogranin A (Chga) locus to homologous regions on mouse chromosome 12 and rat chromosome 6. 840 64

Chromogranins A and B are major soluble proteins in chromaffin granules. Their adrenomedullary content is increased in the spontaneously (genetic) hypertensive rat. Is augmented catecholamine vesicular storage of the chromogranins a specific feature of genetic hypertension? To explore this question, we measured chromogranin A immunoreactivity, using a novel, synthetic peptide radioimmunoassay, in rat adrenal medullas 4-6 weeks after induction of the two-kidney, one clip Goldblatt model of renovascular hypertension and in unmanipulated control animals. We also measured messenger RNAs of chromogranins A and B and dopamine beta-hydroxylase by Northern blot. Immunoreactive adrenal chromogranin A was 3.3-fold higher (p < 0.01) in clipped rat adrenals. Adrenal catecholamine concentrations and phenylethanolamine-N-methyltransferase activity were also higher in clipped rats. Adrenal dopamine beta-hydroxylase activity (both membrane-bound and soluble forms) and corticosterone (glucocorticoid) concentration did not significantly differ between the groups. Adrenal medullary chromogranin A messenger RNA levels in clipped rats were 3.2-fold higher (p = 0.029) than those in the control group, and chromogranin B messenger RNA levels were 4.6-fold higher (p = 0.05). Dopamine beta-hydroxylase messenger RNA levels were 2.9-fold higher (p = 0.038). Thus, augmented synthesis and storage of adrenomedullary chromogranins A and B, catecholamines, and their biosynthetic enzymes appear to be characteristic of both acquired and genetic hypertension.
Hypertension 1993 May
PMID:Catecholamine secretory vesicles. Augmented chromogranins and amines in secondary hypertension. 849 1

A paraganglioma of the urinary bladder in a 60-year-old woman presented with irritative voiding symptoms, without hematuria or hypertension. Sonography revealed a well-limited ovoid mass of the posterior wall, and cystoscopy showed that it was covered by normally appearing mucosa. Treatment consisted of transurethral resection, and the patient has been followed for 2 years without recurrence. Histologically the lesion consisted of small nests of spindle cells with clear to acidophilic cytoplasm; mitotic activity was inconspicuous. Immunohistochemical analyses revealed that the tumor cells were strongly positive for neuron-specific enolase and chromogranin A, and negative for cytokeratin, vimentin, neurofilaments, glial fibrillary acid protein and HMB 45. Sustentacular cells at the periphery of neoplastic cell clusters were positive for S-100 protein.
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PMID:Paraganglioma of the urinary bladder. 877 25

Clinically unsuspected pheochromocytoma is usually discovered either at autopsy or during surgical intervention for unrelated conditions, despite often enormous neoplastic masses producing and storing catecholamine (CA). In order to assess whether these tumours share some common features we have compiled data for six patients admitted to hospital without previous diagnosis of their pheochromocytoma. The clinical variables and the morphological and immunohistochemical characteristics of the tumours revealed that these cases represented quite different expressions of adrenomedullary neoplasms. They differed not only with respect to nuclear ploidity and overall cytoplasmic morphology but also in catecholamine storage and expression of immunoreactive chromogranin A sequences in the intact tissue. In two of the patients hypertension had been overlooked as a diagnostic indicator of their CA-producing tumours. There was no clear relationship between the mean arterial pressure, the tumour content of CA and the serum levels of CA. Processed chromogranin A dominated in the serum of the two hypertensive cases. The 24-h urine values of CA and its main metabolite (vanillin mandelic acid) were, together with the serum values of chromogranin A and B, proportional to tumour mass and provided the most reliable diagnostic indicators for the non-hypertensive as well as the hypertensive cases.
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PMID:Human pheochromocytoma: different patterns of catecholamines and chromogranins in the intact tumour, urine and serum in clinically unsuspected cases. 890 13

Previous studies from our laboratory have demonstrated that the Y chromosome from the spontaneously hypertensive rat (SHR) is responsible for a significant portion of the elevated blood pressure and also produces an earlier pubertal rise in plasma testosterone. We performed the following studies to determine whether the SHR Y chromosome raises blood pressure by sympathetic nervous system responses as measured by adrenal chromogranin A and plasma and tissue catecholamines. Male SHR from the University of Akron colony were studied from 5 to 20 weeks of age. Blood pressure was measured by tail-cuff, tail artery cannulation, and aortic telemetry (Data Sciences); acute (air stress) and chronic (territorial colony) social stressors were compared; blood was collected for determination of plasma catecholamines; and adrenal glands were analyzed at 15 weeks for catecholamines. Rats with the SHR Y chromosome had higher blood pressure and plasma norepinephrine than those with the normotensive Wistar-Kyoto (WKY) Y chromosome. However, the SHR Y chromosome did not significantly change responsiveness to acute or chronic stressors. Phentolamine and clonidine prevented the stress responses. Adrenal chromogranin A levels were elevated 37% and 40% and adrenal norepinephrine content 29% and 100% at 4 and 10 weeks of age, respectively, in rats with an SHR Y chromosome compared with WKY. Chemical sympathectomy normalized blood pressure in all strains and significantly reduced norepinephrine (36% to 41%) in all strains except in WKY, which already had a normal blood pressure. In conclusion, the SHR Y chromosome appears to increase the chronic sympathetic nervous system. A potential mechanism could be a Y locus that influences chronic sympathetic nervous system activity, which may reinforce neurohumoral factors and structural components of the vessel wall, accelerating the development of hypertension.
Hypertension 1997 Feb
PMID:Spontaneously hypertensive rat Y chromosome increases indexes of sympathetic nervous system activity. 904 Apr 47

This report presents the clinical, laboratory, imaging, and pathologic findings in 61 dogs with pheochromocytoma by retrospective evaluation of medical records. Pheochromocytomas were diagnosed by histopathologic examination of tissue specimens in all dogs. Special stains (chromogranin A and synaptophysin) also were used to confirm the chromaffin cell origin of the tumors. Epidemiologic findings were in agreement with previous studies, indicating that pheochromocytomas affect middle-aged to older dogs with no apparent gender or breed predilection. The tumor was considered clinical in 21 dogs (34%), was responsible for abnormalities related to a space-occupying mass in 7 dogs (11%), and was an incidental finding in 35 dogs (57%). The hematologic and biochemical findings were nonspecific. Hypertension was detected in 10 of 23 (43%) dogs tested, but all hypertensive dogs had concurrent diseases that may have contributed to hypertension. Abdominal ultrasonography was the most commonly used imaging procedure, with a mass detected in the region of the adrenal glands in 20 of 40 (50%) dogs examined. In 4 of the 20 dogs (20%), invasion of the caudal vena cava was identified. Surgery was performed in 17 dogs (28%) with immediate death or euthanasia of 5 dogs. Survival after surgery ranged from 1 day to 3.25 years. Pheochromocytomas were locally invasive in 39% of affected dogs and produced metastases in 13% of the cases. Common sites for metastases included regional lymph nodes, liver, lung, kidney, spleen, and bone. A high frequency of concurrent neoplasia (54%), including endocrine neoplasia, was identified.
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PMID:Pheochromocytoma in dogs: 61 cases (1984-1995). 934 93

Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a potent endogenous secretagogue for chromaffin cells. We previously reported that PACAP coupled to the PAC1 receptor to evoke dihydropyridine-sensitive early (15 to 20 minutes) catecholamine secretion and cAMP response element binding protein-mediated trans-activation of the secretory protein chromogranin A promoter in PC12 pheochromocytoma cells. In this report, we studied whether the secretory and transcriptional responses elicited by PACAP were subject to desensitization. We found that PACAP evoked distinct immediate (initial, 0 to 20 minutes) and long-lasting (20 to 180 minutes) effects on catecholamine secretion. Initial secretory and chromogranin A trans-activation responses induced by PACAP were desensitized in a dose-dependent fashion after preexposure of cells to PACAP, and the IC(50) doses of PACAP for desensitization were approximately 18- to approximately 32-fold lower than the EC(50) activating doses for secretion or transcription. Desensitization of the initial secretion response was associated with decreased Ca(2+) influx through L-type voltage-operated Ca(2+) channels. Acute exposure to PACAP also triggered long-lasting (up to 3 hours), extracellular Ca(2+)-dependent, pertussis toxin-insensitive catecholamine secretion; indeed, even after short-term (20 minutes) exposure to PACAP and removal of the secretagogue, PC12 cells continued to secrete norepinephrine up to 76.9+/-0.22% of cellular norepinephrine content after 3 hours. A phospholipase C-beta inhibitor (U-73122) blocked this extended secretory response, which was dependent on low-magnitude Ca(2+) influx resistant to several L-, N-, P/Q-, or T-type Ca(2+) channel antagonists, but sensitive to Zn(2+), Ni(2+), Cd(2+), or to the store-operated Ca(2+) channel blocker SKF96365. A less than additive effect of the sarco-endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin plus PACAP on this sustained secretion also supported a contribution of store-operated Ca(2+) entry to the sustained secretory response. We propose that PACAP-evoked secretion and transcription are subject to homologous desensitization in PC12 cells; however, PACAP also induces long-lasting secretion, even under dose and time circumstances in which acute, dihydropyridine-sensitive secretion has been desensitized. Although initial secretion is mediated by an L-type voltage-operated Ca(2+) channel, extended secretion may involve a store-operated Ca(2+) channel that is activated through a G(q/11)/phospholipase C-beta/phosphoinositide signaling pathway.
Hypertension 1999 Nov
PMID:Time-dependent effects of the neuropeptide PACAP on catecholamine secretion : stimulation and desensitization. 1056 98


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