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

Laparoscopic adrenalectomy has been recommended as the standard method for removing an aldosteronoma. To assess our surgical experience with primary hyperaldosteronism in the era of laparoscopic adrenalectomy a 6-year retrospective review of 30 consecutive patients was done. The 20 men and 10 women ranged in age from 35 to 78 with a mean of 51.2 years. All patients were hypertensive and hypokalemic with a mean serum potassium of 2.9 +/- 0.32 (standard deviation) mmol/L. Serum aldosterone was elevated in 28 of 30 (94%) patients and normal in the remaining two. Serum renin was suppressed in all patients. CT correctly localized the tumor in all 30 patients. Twenty-eight patients had histologically documented adenomas and two had associated cortical hyperplasia on pathology. Mean adenoma size was 2.0 +/- 1.12 cm. Twenty-four patients underwent left laparoscopic adrenalectomies, whereas right laparoscopic adrenalectomies were performed in five. One was converted to an open left adrenalectomy. Mean operative time was 183 minutes. The mean hospital stay for laparoscopic adrenalectomy was 2.2 days. The patients were followed from one to 63 months (mean 26.1 months). Twenty-nine of 30 (95%) patients were rendered normokalemic. The remaining patient takes a potassium-wasting diuretic. Persistent hypertension was present in 10 of 30 (33%) patients. Blood pressure in nine of 10 patients was controlled with less medical therapy. The other patient's blood pressure remained difficult to control despite multiple medications. Duration of hypertension before surgery was a significant risk factor for persistent hypertension (P < 0.05). Gender (P > 0.05) and age (P > 0.05) at the time of surgery were not statistically significant predicators for persistent hypertension. There were two reported trocar site hernias. We conclude that primary hyperaldosteronism due to aldosterone-producing tumors can be diagnosed and accurately localized with preoperative measurements of serum aldosterone, renin, and CT scanning. Laparoscopic adrenalectomy is safe and effective for the treatment of primary hyperaldosteronism with minimal associated morbidity and a short hospital stay. Hypokalemia may be cured by surgical treatment, although persistent hypertension still occurs. Duration of hypertension before surgery is a risk factor for persistent hypertension whereas age and sex are not.
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PMID:Primary hyperaldosteronism in the era of laparoscopic adrenalectomy. 1189 3

The epithelial Na+ channel (ENaC) forms the pathway for Na+ absorption in the kidney collecting duct and other epithelia. Dominant gain-of-function mutations cause Liddle's syndrome, an inherited form of hypertension resulting from excessive renal Na+ absorption. Conversely, loss-of-function mutations cause pseudohypoaldosteronism type I, a disorder of salt wasting and hypotension. Thus, ENaC has a critical role in the maintenance of Na+ homeostasis and blood pressure control. Altered Na+ absorption in the lung may also contribute to the pathogenesis of cystic fibrosis. Epithelial Na+ absorption is regulated in large part by mechanisms that control the expression of ENaC at the cell surface. Nedd4, a ubiquitin protein ligase, binds to ENaC and targets the channel for endocytosis and degradation. Liddle's syndrome mutations disrupt the interaction between ENaC and Nedd4, resulting in an increase in the number of ENaC channels at the cell surface. Aldosterone and vasopressin also regulate Na+ absorption to defend against hypotension and hypovolemia. Both hormones increase the expression of ENaC at the cell surface. The goal of this review is to summarize recent data on the regulation of ENaC expression at the cell surface.
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PMID:The epithelial Na+ channel: cell surface insertion and retrieval in Na+ homeostasis and hypertension. 1194 47

Although the aldosterone-responsive segments of the nephron together reabsorb <10% of the filtered Na+, certain single-gene defects that affect the epithelial Na+ channel (ENaC) in the luminal membrane of the collecting duct (CD) or its regulation by aldosterone cause severe hypertension, whereas others cause salt wasting and hypotension. These rare defects illustrate the key role of the distal nephron in maintaining normal extracellular volume and blood pressure. Genetic defects that increase the Cl- conductance of the junctional complexes may also lead to salt retention and hypertension. Less dramatic alterations in regulatory actions of other hormones such as vasopressin (VP), either alone or with other genetic variations, diet, or environmental factors, may also produce Na+ retention or loss. Although VP acts primarily to regulate water balance, it is also an antinatriuretic hormone. Elevated basal plasma VP levels, and/or augmented VP release with increased Na+ intake, have been linked to essential hypertension in humans and in animal models of congestive heart failure and cirrhosis. Norepinephrine, dopamine, and prostaglandin E2 can inhibit the antinatriuretic effects of VP, and changes in the actions of these autocrine and paracrine regulators may also be involved in abnormal regulation of Na+ reabsorption.
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PMID:Abnormal regulation of ENaC: syndromes of salt retention and salt wasting by the collecting duct. 1211 May 5

The epithelial sodium channel (ENaC) present in the kidney collecting duct, distal colon, and the lung is responsible for salt reabsorption and whole body volume regulation. It is composed of three homologous subunits, alpha, beta, and gamma, and mutations to these subunits can lead to the salt wasting disease pseudohypoaldosteronism type I, associated with decreased channel density at the plasma membrane or to the hypertensive disorder, Liddle's syndrome, in which channel residency time at the plasma membrane is enhanced. Regulation of ENaC trafficking and turnover is therefore critical to sodium homeostasis. In this study we examined whether ENaC is present in the cholesterol-enriched microdomains commonly called lipid rafts, in the endogenously expressing A6 cell line. We demonstrate that a fraction of alpha, beta, and gamma ENaC is present in detergent-insoluble membranes, that subunits exist in membranes that float on discontinuous sucrose density gradients, and that methyl-beta-cyclodextrin treatment causes a redistribution of ENaC subunits to higher density membranes. Furthermore, chronic aldosterone stimulation results in a shift in the membrane density of all three subunits. Biotinylation of apical membrane proteins revealed that ENaC is present in lipid rafts on the plasma membrane. In conclusion, these results show that ENaC is present in lipid rafts both intracellularly and on the cell surface. Raft association may be important for trafficking and/or function of the channel.
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PMID:Endogenously expressed epithelial sodium channel is present in lipid rafts in A6 cells. 1216 33

The epithelial sodium channel (ENaC) is a membrane protein made of three different but homologous subunits (a, b, and g) present in the apical membrane of epithelial cells of, for example, the distal nephron. This channel is responsible for salt reabsorption in the kidney and can cause human diseases by increasing channel function in Liddle's syndrome, a form of hereditary hypertension, or by decreasing channel function in pseudohypoaldosteronism type I, a salt-wasting disease in infancy. This review briefly discusses recent advances in understanding the implication of ENaC in Liddle's syndrome and in pseudohypoaldosteronism type I, both caused by mutations in the SCNN1 (ENaC) genes. Furthermore, it is still an open question to which extent SCNN1 genes coding for ENaC might be implicated in essential hypertension. The development of Scnn1 genetically engineered mouse models will provide the opportunity to test the effect of environmental factors, like salt intake, on the development of this kind of salt- sensitive hypertension.
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PMID:Epithelial sodium channel, salt intake, and hypertension. 1253 Sep 30

Long-term licorice ingestion is a well-known cause of secondary hypertension and hypokalemia. Nevertheless, its initial presentation with a very severe degree of hypokalemia and paralysis is exceedingly rare. We report an elderly Asian man who presented to the emergency department with marked muscle weakness that progressed to paralysis. His blood pressure was 160/96 mm Hg. The major biochemical abnormalities were hypokalemia (plasma K+ concentration, 1.8 mmol/L) and metabolic alkalosis (HCO - 3 , 36 mmol/L). His renal potassium excretion was higher (transtubular potassium gradient of 9). Plasma renin activity and aldosterone concentration were suppressed and cortisol concentration was normal. A detailed history revealed that he had ingested tea flavored with 100 g of natural licorice root containing 2.3% glycyrrhizic acid daily for 3 years. Note that renal potassium wasting and hypertension persisted for 2 weeks after discontinuing licorice consumption along with KCl supplement and spironolactone. Long-term licorice ingestion should be kept in mind as a cause of paralysis with an extreme degree of hypokalemia to avoid missing this recognizable and curable medical disorder.
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PMID:An unusual cause of hypokalemic paralysis: chronic licorice ingestion. 1264 Feb 91

The epithelial Na+ channel (ENaC) is the apical entry pathway for Na+ in many Na+-reabsorbing epithelia. ENaC is a heterotetrameric protein composed of homologous alpha, beta, and gamma subunits. Mutations in ENaC cause severe hypertension or salt wasting in humans; and consequently, ENaC activity is tightly controlled. According to the concept of Na+ self-inhibition, the extracellular Na+ ion itself can reduce ENaC activity. The molecular basis for Na+ self-inhibition is unknown. Here, we describe cloning of a new ENaC subunit from Xenopus laevis (epsilonxENaC). epsilonxENaC can replace alphaxENaC and formed functional, highly selective, amiloride-sensitive Na+ channels when coexpressed with betaxENaC and gammaxENaC. Channels containing epsilonxENaC showed strong inhibition by extracellular Na+. This Na+ self-inhibition was significantly slower than for alphaxENaC-containing channels. Using site-directed mutagenesis, we show that the proximal part of the large extracellular domain controls the speed of self-inhibition. This suggests that this region is involved in conformational changes during Na+ self-inhibition.
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PMID:A new subunit of the epithelial Na+ channel identifies regions involved in Na+ self-inhibition. 1276 46

Magnesium plays an essential role in many biochemical and physiological processes. Homeostasis of magnesium is tightly regulated and depends on the balance between intestinal absorption and renal excretion. During the last decades, various hereditary disorders of magnesium handling have been clinically characterized and genetic studies in affected individuals have led to the identification of some molecular components of cellular magnesium transport. In addition to these hereditary forms of magnesium deficiency, recent studies have revealed a high prevalence of latent hypomagnesemia in the general population. This finding is of special interest in view of the association between hypomagnesemia and common chronic diseases such as diabetes, coronary heart disease, hypertension, and asthma. However, valuable methods for the diagnosis of body and tissue magnesium deficiency are still lacking. This review focuses on clinical and genetic aspects of hereditary disorders of magnesium homeostasis. We will review primary defects of epithelial magnesium transport, disorders associated with defects in Ca(2+)/ Mg(2+) sensing, as well as diseases characterized by renal salt wasting and hypokalemic alkalosis, with special emphasis on disturbed magnesium homeostasis.
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PMID:Genetics of hereditary disorders of magnesium homeostasis. 1463 61

Congenital adrenal hyperplasia (CAH) refers to a family of inherited disorders of adrenal steroidogenesis in which each disorder is characterized by a specific enzyme deficiency that impairs cortisol production by the adrenal cortex. The enzymes most commonly affected are 21-hydroxylase (21-OH), 11beta-hydroxylase, 3beta-hydroxysteroid dehydrogenase, and less often, 17alpha-hydroxylase/17,20-lyase and cholesterol desmolase. Many of the corresponding genes for the described enzymes have been isolated and characterized, and specific mutations causing CAH have been identified. In classical CAH (simple virilizing and salt wasting forms), androgen excess causes external genital ambiguity in newborn females and progressive postnatal virilization in both sexes. In nonclassical CAH, 21-OHD is partial and occurs with milder symptoms. A deficiency of 11beta-Hydroxylase deficiency results in ambiguous genitalia in the newborn genetic female and androgen excess and hypertension in both males and females. In 3beta-hydroxysteroid deficiency adrenal and gonadal androgen production is deficient resulting in incomplete genital development in genetic males and limited androgen affect in females. Two less frequent causes of CAH 17alpha-Hydroxylase/17,20-lyase and cholesterol desmolase result in external female genitalia in both sexes. Hormonal diagnosis is described for each disorder.
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PMID:Inborn errors of adrenal steroidogenesis. 1465 79

Glucocorticoid remediable aldosteronism (GRA) appears to be the most common monogenic form of human hypertension. As a result of chimeric gene duplication, aldosterone is ectopically synthesized in the zona fasciculata of the adrenal gland under the control of adrenocorticotropin (ACTH). Affected individuals are typically hypertensive, often with onset in youth, and demonstrate refractoriness to standard antihypertensives such as angiotensin-converting enzyme inhibitors and beta-blockers. GRA subjects are normokalemic but often develop hypokalemia when treated with a potassium-wasting diuretic. Analysis of affected kindreds has demonstrated a high prevalence of early cerebral hemorrhage, largely as a result of aneurysms. Identification of affected individuals should allow direct neurovascular screening and targeted antihypertensive therapy.
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PMID:Glucocorticoid-remediable aldosteronism. 1466 64


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