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

The paper is aimed at evaluation of certain indices of cellular immunity in pregnant women with gestosis superimposing pre-existing renal diseases and comparing them with the immunological condition of women with essential gestosis. T lymphocyte subpopulations and lymphocyte proliferative responses to mitogens (phytohemagglutinin--PHA, concanavalin A--Con A and pokeweed mitogen--PWM) in the fetal calf serum and autological sera were studied. The groups of examined pregnant women in the 3rd trimester did not vary with regard to gestation age, calendar age and to the severity of edema (E), proteinuria (P) and hypertension (H) gestosis symptoms. It has been found that equal changes occur in both groups of women, regarding the examined indices of cellular immunity, when referred to normal pregnant women. In the gestotic women a decreased absolute and percentage content of CD8+ T cells and increased percentage of CD3+ and CD4+ lymphocytes were found in comparison with the normal pregnant women, which led to an almost 2.5-fold increase of CD4+/CD8+ ratio. The sera of gestotic women, in comparison with the healthy pregnant group, strongly increased the proliferation of Con A and PWM-induced lymphocytes. It may then be assumed that the observed immunological changes do not coincide with the primary causes of gestosis. We suggest that immunological factors largely contribute to the development of essential gestosis and gestosis superimposing pre-existing renal disease.
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PMID:Essential edema-proteinuria-hypertension (EPH) gestosis and gestosis superimposing pre-existing renal disease: comparison of cellular immunity parameters. 857 97

The amiloride-sensitive epithelial sodium channel (ENaC) controls sodium reabsorption in the distal nephron. Its activity is under the control of aldosterone. The genes encoding ENaC have been identified and revealed an heteromultimeric structure of the protein composed of three homologous alpha beta gamma subunits. The role of ENaC in the pathogenesis of hypertension has been demonstrated by complete linkage of the gene encoding the beta and gamma subunits to an autosomal form of salt-sensitive hypertension. Analysis of these genes from patients affected by a sever hypertension (Liddle syndrome) identified mutations in the carboxy-terminus of ENaC subunits causing channel hyperactivity, consistent with increased sodium reabsorption in the distal nephron. Pseudohypoaldosteronism type-1 (PHA-1) represents a hereditary form of salt-loosing nephropathy characterized by hyperkalemia, dehydration and metabolic acidosis. Analysis of genes encoding ENaC subunits in patients affected by PHA-1 identified different types of mutations causing loss of function or a decrease in ENaC channel activity. These studies demonstrated the critical role of ENaC channel in the maintenance salt and extracellular fluid balance, and regulation of blood pressure.
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PMID:The ENaC channel as the primary determinant of two human diseases: Liddle syndrome and pseudohypoaldosteronism. 898 44

The periaqueductal gray matter (PAG) has been implicated in a variety of different functions, including autonomic regulation. Chemical stimulation of the lateral PAG produces hypertension and tachycardia while activation of the ventrolateral PAG produces the opposite effect. While these effects are the result of alterations in sympathetic activity, little is known about whether the PAG can modulate vagal functions as well. The anterograde axonal tracing method using the plant lectin Phaseolus vulgaris leucoagglutinin (PHA-L) was used to determine whether both of the lateral and ventrolateral PAG columns project to vagal preganglionic neurons and/or to the nucleus tractus solitarius (NTS). Highly restricted PHA-L injections were made in all four PAG columns throughout their rostrocaudal extent in rats. Labeled fibers were visualized by immunohistochemistry and studied in relationship with choline acetyltransferase (ChAT) immunostained parasympathetic preganglionic neurons of the dorsal motor vagal nucleus (DMV) and nucleus ambiguous (NA). The lateral PAG projects to the lateral DMV and to the caudal part of the external NA. The ventrolateral PAG innervates the same regions and also projects to the rostral part of the external NA -- a site that contains cardiac parasympathetic preganglionic neurons. Both the lateral and ventrolateral PAG project to the NTS in a similar fashion innervating the medial, ventrolateral and commissural subnuclei. In summary, the lateral and ventrolateral PAG have similar patterns of innervation of the NTS and DMV, but their projection to the NA is different: the rostral external NA receives innervation only from the ventrolateral PAG and the lateral PAG innervates the caudal part.
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PMID:Periaqueductal gray matter projection to vagal preganglionic neurons and the nucleus tractus solitarius. 929 20

The kidney plays a dominant role in maintaining sodium homeostasis. Despite wide variation in environmental exposure, the osmolality of the extracellular fluid that is determined by the sodium ion concentration is maintained within narrow margins. Derangement in function of proteins that transport Na+ and of those regulating the activity of these sodium-transporting proteins are likely to be responsible for a number of clinical disorders of fluid and electrolyte homeostasis. The amiloride-sensitive epithelial sodium channel (ENaC) is implicated in the control of blood pressure as demonstrated by the analysis of two genetic diseases, Liddle's syndrome and pseudohypoaldosteronism (PHA-1). Mutations have been identified in the genes coding for the alpha-, beta- or gamma-subunit of ENaC. ENaC constitutes the limiting step for sodium reabsorption in epithelial cells that line the distal nephron, distal colon, ducts of several exocrine glands and lung airways and might play an important role in pathophysiological and clinical conditions such as hypertension or lung edema.
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PMID:Reversal of convention: from man to experimental animal in elucidating the function of the renal amiloride-sensitive sodium channel. 969 87

Aldosterone participates in blood volume and serum potassium homeostasis, which in turn regulate aldosterone secretion by the zona glomerulosa of the adrenal cortex. Autonomous aldosterone hypersecretion leads to hypertension and hypokalemia. Improved screening techniques have led to a re-evaluation of the frequency of primary aldosteronism among adults with hypertension, recognizing that normokalemic cases are more frequent than was previously appreciated. The genetic basis of glucocorticoid remediable aldosteronism has been elucidated and adequately explains most of the pathophysiologic features of this disorder. A new form of familial aldosteronism has been described, familial hyperaldosteronism type II; linkage analysis and direct mutation screening has shown that this disorder is unrelated to mutations in the genes for aldosterone synthase or the angiotensin II receptor. The features of aldosterone hypersecretion may be due to non-aldosterone-mediated mineralocorticoid excess. These include two causes of congenital adrenal hyperplasia (11 beta-hydroxylase deficiency and 17 alpha-hydroxylase deficiency), the syndrome of apparent mineralocorticoid excess (AME) due to 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) deficiency, primary glucocorticoid resistance, Liddle's syndrome due to activating mutations of the renal epithelial sodium channel, and exogenous sources of mineralocorticoid, such as licorice, or drugs, such as carbenoxolone. The features of mineralocorticoid excess are also often seen in Cushing's syndrome. Hypoaldosteronism may lead to hypotension and hyperkalemia. Hypoaldosteronism may be due to inadequate stimulation of aldosterone secretion (hyporeninemic hypoaldosteronism), defects in adrenal synthesis of aldosterone, or resistance to the ion transport effects of aldosterone, such as are seen in pseudohypoaldosteronism type I (PHA I). PHA I is frequently due to mutations involving the amiloride sensitive epithelial sodium channel. Gordon's syndrome (PHA type II) is due to resistance to the kaliuretic but not sodium reabsorptive effects of aldosterone for which the genetic basis is still unknown. This review aims to provide a survey of the clinical disorders of aldosterone excess and deficiency and their clinical management, with a focus on primary aldosteronism and isolated aldosterone deficiency.
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PMID:Hyper- and hypoaldosteronism. 1023 50

Arterial blood pressure is critically dependent on sodium balance. The kidney is the key player in maintaining sodium homeostasis. Aldosterone-dependent epithelial sodium transport in the distal nephron is mediated by the highly selective, amiloride-sensitive epithelial sodium channel (ENaC). Direct evidence that dysfunction of ENaC participates in blood pressure regulation has come from the molecular analysis of two human genetic diseases, Liddle's syndrome and pseudohypoaldosteronism type 1 (PHA-1). Both, increased sodium reabsorption despite low aldosterone levels in Liddle's patients and decreased sodium reabsorption despite high aldosterone levels in PHA-1 patients, demonstrated that ENaC is an effector for aldosterone action. Gene-targeting and classical transgenic technology enable the generation of mouse models for these diseases and the analysis of the involvement of the epithelial sodium channel (ENaC) in the progress of these diseases. A first mouse model using alphaENaC transgenic knockout mice [alphaENaC(-/-)Tg] mimicked several clinical features of PHA-1, like salt-wasting, metabolic acidosis, high aldosterone levels, growth retardation and increased early mortality. Such mouse models will be necessary in testing the involvement of genetic and/or environmental factors like salt-intake in hypertension.
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PMID:Implication of ENaC in salt-sensitive hypertension. 1041 16

The highly amiloride-sensitive epithelial sodium channel (ENaC) is an apical membrane constituent of cells of many salt-absorbing epithelia. In the kidney, the functional relevance of ENaC expression has been well established. ENaC mediates the aldosterone-dependent sodium reabsorption in the distal nephron and is involved in the regulation of blood pressure. Mutations in genes encoding ENaC subunits are causative for two human inherited diseases: Liddle's syndrome, a severe form of hypertension associated with ENaC hyperfunction, and pseudohypoaldosteronism (PHA-1), a salt-wasting syndrome caused by decreased ENaC function. Transgenic mouse technologies provide a useful tool to study the role of ENaC in vivo. Different mouse lines have been established in which each of the ENaC subunits was affected. The phenotypes observed in these mice demonstrated that each subunit is essential for survival and for regulation of sodium transport in kidney and colon. Moreover, the alpha subunit plays a specific role in the control of fluid absorption in the airways at birth. Such mice can now be used to study the role of ENaC in various organs and can serve as models to understand the pathophysiology of these human diseases.
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PMID:Dysfunction of epithelial sodium transport: from human to mouse. 1076 60

The epithelial sodium channel (ENaC) expressed in aldosterone-responsive epithelial cells of the kidney and colon plays a critical role in the control of sodium balance, blood volume, and blood pressure. In lung, ENaC has a distinct role in controlling the ionic composition of the air-liquid interface and thus the rate of mucociliary transport. Loss-of-function mutations in ENaC cause a severe salt-wasting syndrome in human pseudohypoaldosteronism type 1 (PHA-1). Gain-of-function mutations in ENaC beta and gamma subunits cause pseudoaldosteronism (Liddle's syndrome), a severe form of salt-sensitive hypertension. This review discusses genetically defined forms of a salt sensitivity and salt resistance in human monogenic diseases and in animal models mimicking PHA-1 or Liddle's syndrome. The complex interaction between genetic factors (ENaC mutations) and the risk factor (salt intake) can now be studied experimentally. The role of single-nucleotide polymorphisms (SNPs) in determining salt sensitivity or salt resistance in general populations is one of the main challenges of the post-genomic era.
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PMID:Epithelial sodium channel and the control of sodium balance: interaction between genetic and environmental factors. 1182 91

Mutations in WNK kinases cause pseudohypoaldosteronism type II (PHA II) and may represent a novel signaling pathway regulating blood pressure and K(+) and H(+) homeostasis. PHA II is an autosomal dominant disorder characterized by hypertension, hyperkalemia, and metabolic acidosis, with normal glomerular filtration rate. Thiazide diuretics correct all abnormalities. Inactivating mutations in the thiazide-sensitive NaCl cotransporter cause Gitelman syndrome, featuring hypotension, hypokalemia, and metabolic alkalosis plus hypocalciuria and hypomagnesemia. We investigated whether hypercalciuria and hypermagnesemia occurred in a large family with PHA II. Eight affected and eight unaffected members of a PHA II family with the Q565E WNK 4 mutation were studied. In affected members blood and urinary chemistry were measured on and off hydrochlorothiazide (HCTZ), and bone mineral density was determined. Marked sensitivity to HCTZ was found. A mean dose of 20 mg/d reduced mean blood pressure in the six hypertensive subjects by 54.3 (systolic) and 24.5 (diastolic) mm Hg. In affected subjects, HCTZ reduced mean serum K(+) by 1.12 mmol/liter, mean serum Cl(-) by 6.2 mmol/liter, and mean urinary calcium by 65% and elevated mean serum calcium by 0.11 mmol/liter and mean serum urate by 118 micromol/liter. Compared with the literature, this represents an increase of 6-7 in HCTZ potency. Affected members had normomagnesemia, hypercalciuria (336 +/- 113 vs. 155 +/- 39 mg/d in unaffected relatives, P = 0.0002), and decreased bone mineral density. In PHA II the observed marked sensitivity to thiazides and the hypercalciuria are consistent with increased NaCl cotransporter activity. PHA II may serve as a model to investigate thiazides' beneficial effects and side effects.
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PMID:Pseudohypoaldosteronism type II: marked sensitivity to thiazides, hypercalciuria, normomagnesemia, and low bone mineral density. 1210 33

Primary hyperaldosteronism represents less tha 1% of all causes of hypertension. We report one case of primary hyperaldosteronism which emphasizes the difficulty of distinguishing tumoral PHA from idiopathic PHA (bilateral adrenal hyperplasia), observed in a 57-year-old man. The diagnosis was suggested by marked hypokalemia, and was confirmed by hyperaldosteronaemia and low and poorly stimulated renin activity. Intravenous saline infusion failed to significantly suppress plasma aldosterone levels. Upright posture for 60 minutes suppressed plasma aldosterone concentration. A Computed tomography (CT) scan showed bilateral adrenal mass. Management consisted of total right adrenalectomy, and enucleation of adenoma from the opposite adenoma. The patient is normotensive 4 years after surgery.
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PMID:[Bilateral Conn's adenoma. Diagnostic discussions]. 1246 32


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