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)

The epithelial Na+ channel (ENaC) controls the rate-limiting step in the process of transepithelial Na+ reabsorption in the distal nephron, the distal colon, and the airways. Hereditary salt-losing syndromes have been ascribed to loss of function mutations in the alpha-, beta-, or gamma-ENaC subunit genes, whereas gain of function mutations (located in the COOH terminus of the beta- or gamma-subunit) result in hypertension due to Na+ retention (Liddle's syndrome). In mice, gene-targeting experiments have shown that, in addition to the kidney salt-wasting phenotype, ENaC was essential for lung fluid clearance in newborn mice. Disruption of the alpha-subunit resulted in a complete abolition of ENaC-mediated Na+ transport, whereas knockout of the beta- or gamma-subunit had only minor effects on fluid clearance in lung. Disruption of each of the three subunits resulted in a salt-wasting syndrome similar to that observed in humans.
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PMID:Genetic disorders of membrane transport. V. The epithelial sodium channel and its implication in human diseases. 1007 30

The medical care of chronic renal failure patients is often complicated by the comorbid conditions of hypertension and coronary artery disease in the perioperative period. The limitations on solute and water excretion imposed by renal dysfunction increase the susceptibility of this population to both salt deficit and surfeit, as well as hyponatremia and hypernatremia perioperatively. Accurate assessment and successful treatment of these complications in renal failure patients require understanding of the concept of electrolyte-free water, proper utilization of diuretics, and calculated prescription of fluid therapy. The presence of hyperkalemia in the adapted renal failure patient generally indicates a severe reduction in glomerular filtration, such that nonrenal hypokalemic treatments are imperative. IV calcium-based therapy and infusion of insulin with glucose represent the mainstays of immediate therapy, and sodium bicarbonate therapy should be given only when severe acidemia is present. Perioperative aggravation of preexistent hypertension is common. Rebound hypertension attributable to injudicious adjustment of the medical regimen should be diligently searched for first, before any new therapies are recommended. Relief of pain or anxiety may be all that is necessary. Briefly acting calcium channel blocker therapy should not be employed in these cases, and smooth IV control by a variety of agents is preferable, the choice of the agent contingent on the clinical scenario.
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PMID:Selective review of key perioperative renal-electrolyte disturbances in chronic renal failure patients. 1033 49

The case of a 74-year-old woman with past history of hypertension and cerebrovascular accident admitted with pneumonia, dehydration, hypernatremia and severe hypokalemic alkalosis is presented. After correction of the hypertonic dehydration, the hypokalemia and alkalosis persisted in spite of aggressive potassium supplementation and the patient became hypertensive. Mineralocorticoid excess was suspected and excluded after extensive endocrinological testing. The use of aldactone failed to revert the abnormalities. Triamterene administration corrected the electrolytes and acid base aberrations, and dramatically improved the blood pressure control. This clinical picture is compatible with the diagnosis of Liddle's syndrome. Our patient exemplifies the unique occurrence of hypokalemic metabolic alkalosis in association with volume contraction at the start of the hospitalization and volume expansion later on her course.
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PMID:Saline-resistant metabolic alkalosis, severe hypokalemia and hypertension in a 74-year-old woman. 1066 85

Advancing age is usually accompanied by a decline in glomerular filtration rate and an increased incidence of certain renal and electrolyte disorders. These include an increased susceptibility to acute renal failure, hypo- and hypernatremia, hyperkalemia, and hypertension. This report discusses anatomic and physiological observations related to the aged human kidney and explores the various theories and postulated mechanisms underlying these changes.
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PMID:Biology of renal aging in humans. 1067 14

The kidney regulates sodium metabolism with extraordinary precision and sensitivity. This is accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between anti-natriuretic and natriuretic factors. Dopamine, produced in renal proximal tubule cells, plays a central role in this interactive network. Natriuretic hormones that are released from extrarenal sources, such as atrial natriuretic peptide, mediate some of their effects via renal dopamine receptors. On the level of the tubules, dopamine acts by opposing the effects of anti-natriuretic factors, such as angiotensin II and alpha-adrenergic receptors. Sodium retention leads to an increase in renal dopamine tonus, and the natriuretic effects of dopamine are more prominent under this condition. Inhibition or down-regulation of dopamine receptors significantly attenuates the natriuretic response to salt loading. Renal dopamine is modulated by the supply of filtered L-DOPA and the metabolism of dopamine via catechol-O-methyldopamine. The importance of dopamine as a natriuretic hormone is reflected by its capacity to inhibit the majority of renal tubule sodium transporters. Notably, the activity of Na+, K+ ATPase is inhibited in most tubule segments by dopamine. Recent studies have elucidated many of the signaling pathways for renal dopamine receptors. Novel principles for homologous and heterologous sensitization of dopamine receptors have been detected that may explain some of the interaction between dopamine and other first messengers that modulate renal tubule sodium transport. A broad understanding of the renal dopamine system has become increasingly important, since there is now strong evidence from both clinical and experimental studies that dysregulation of the renal dopamine system plays a role in many forms of multigenetic hypertension.
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PMID:Intrarenal dopamine: a key signal in the interactive regulation of sodium metabolism. 1084 5

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

There are five types of oedema: vasogenic, cytotoxic, interstitial, hyperemic and osmotic. The differences lie on the type and localization of the oedema, the state of the blood-brain barrier (BBB) and the pathological context. Under physiological conditions, the osmolarity of extra cellular fluids (ECFs) is equal on both sides of the BBB. However, the pathophysiological variations of circulating osmolarity (including acute hyponatremia and hypernatremia) do not affect, at the same time, the osmolarity of cerebral ECFs. This situation generates an osmotic gradient on either side of the BBB. The latter, if intact, behaves like a semi-permeable membrane allowing water transport according to the osmotic laws. Depending on its direction, water movement could induce cerebral liquid inflation (i.e. osmotic oedema) or cerebral dehydration. In case of osmotic insult, cerebral cell modify their active osmotic molecular contents in order to limit volume variation. There are two types of osmoactive molecules, organic (i.e. ideogenic osmoles: amino acids, polyols and trimethylamines) and non organic (i.e. electrolytes). In the event of plasma hypotonicity, cerebral cells expel active osmotic molecules to reduce the osmotic gradient and water movement thereby reducing edema. The opposite reaction is observed in the case of hypertonic insult. This cerebral osmoregulation becomes more effective, the slower the osmotic disorder. It explains, for example, why patients with chronic and severe hyponatremia could be asymptomatic. Severe osmotic oedema is observed mainly in water intoxication, acute hyponatremia or too rapid reduction of hyperosmolarity. However, osmotic oedema is not limited to extreme clinical circumstances. Hyponatremia, even modest, could modify cerebral blood volume and impair osmoregulation. Generally these minor modifications do not affect normal brain tissue. In the presence of cerebral lesion, osmoregulation operates only in areas of preserved BBB. The pathological zones are therefore exposed to osmotic oedema (even in cases of moderate hyponatremia) with deterioration of both clinical status and intracranial pressure. This authentic phenomenon could be insidious and difficult to differentiate from osmotic central oedema. Hyponatremia constitutes an authentic secondary cerebral insult of systemic origin, an entity clearly identified by experimental studies to justify the choice between crystalloids and colloids in neuroanaesthesia and neurointensive care. These studies have revealed an increase in water content in normal brain tissues after administration of hypotonic solutions. The increase in plasma osmolarity as a treatment modality using mannitol or hypertonic saline is based on the same concepts. The most remote indication is the occurrence of a reactive mydriasis in the context of trauma for example. More recently, therapeutic hypernatremia has been proposed to control intracranial hypertension.
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PMID:[Osmotic cerebral oedema: the role of plasma osmolarity and blood brain barrier]. 1274 89

The progression of renal disease correlates strongly with hypertension and the degree of proteinuria, suggesting a link between excessive Na+ reabsorption and exposure of the proximal tubule to protein. The present study investigated the effects of albumin on cell growth and Na+ uptake in primary cultures of human proximal tubule cells (PTC). Albumin (1.0 mg/ml) increased cell proliferation to 134.1 +/- 11.8% (P < 0.001) of control levels with no change in levels of apoptosis. Exposure to 0.1 and 1.0 mg/ml albumin increased total 22Na+ uptake to 119.1 +/- 6.3% (P = 0.005) and 115.6 +/- 5.3% (P < 0.006) of control levels, respectively, because of an increase in Na+/H+ exchanger isoform 3 (NHE3) activity. This was associated with an increase in NHE3 mRNA to 161.1 +/- 15.1% (P < 0.005) of control levels in response to 0.1 mg/ml albumin. Using confocal microscopy with a novel antibody raised against the predicted extracellular NH2 terminus of human NHE3, we observed in nonpermeabilized cells that exposure of PTC to albumin (0.1 and 1.0 mg/ml) increased NHE3 at the cell surface to 115.4 +/- 2.7% (P < 0.0005) and 122.4 +/- 3.7% (P < 0.0001) of control levels, respectively. This effect was paralleled by significant increases in NHE3 in the subplasmalemmal region as measured in permeabilized cells. These albumin-induced increases in expression and activity of NHE3 in PTC suggest a possible mechanism for Na+ retention in response to proteinuria.
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PMID:Effects of pathophysiological concentrations of albumin on NHE3 activity and cell proliferation in primary cultures of human proximal tubule cells. 1279 7

Lambs exposed in utero to maternal hypertonicity demonstrate plasma hypertonicity and arterial hypertension. To determine whether hypertonicity is due to an altered osmoregulatory set point, we examined arginine-vasopressin and cardiovascular responses to hypertonic saline infusion in these offspring. Study lambs [dehydrated (Dehy)] were exposed to maternal hypernatremia (8-10 mEq/liter increase; 110-150 d gestation) induced by water restriction. Control singleton and Control twins were born to ewes provided ad libitum water. We anticipated reduced birth weight due to maternal dehydration-induced anorexia and therefore included a Control group of twin gestations to approach a similar birth weight near term. After delivery, ewes from all three groups were provided ad libitum water, and their newborns were allowed ad libitum nursing. At 15 +/- 2 d of age, lambs were prepared with bladder and vascular catheters. At 23 +/- 2 d, after a 2-h basal period, neonatal lambs were iv infused with hypertonic 0.83 m NaCl (0.075 ml/kg x h) for 2 h, followed by a 2-h recovery. Neonatal mean arterial pressure and urine flow were continuously monitored, and blood samples were obtained before, during, and after infusion. During the basal period, Dehy neonates and Control twins demonstrated significantly increased plasma sodium levels and mean arterial pressure than Control singletons. In addition, the Dehy neonates had significantly increased plasma osmolality compared with Control singletons and twins. In response to hypertonic infusion, the Dehy offspring continued to exhibit hypertonicity and hypertension. Importantly, plasma tonicity and blood pressure were greatest in Dehy singletons, lowest in singleton controls, and intermediate in twin controls. Furthermore, the plasma osmolality threshold for AVP secretion was significantly higher in Dehy singletons (290 +/- 2 mOsm/kg) than Control twins (285 +/- 1 mOsm/kg) and Control singletons (280 +/- 2 mOsm/kg), indicating in utero programming of an altered set point for systemic osmolality and blood pressure regulation. Because both twin gestation and dehydration-anorexia incur potential fetal nutritional stress, the results suggest that both in utero hypertonicity and nutrition reduction contribute to offspring programming. We postulate that the nutritional stress associated with twins (as well as dehydration-induced anorexia) contributes to increased plasma sodium levels, whereas the increased plasma osmolality is due to in utero hypertonicity.
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PMID:Programming of hypertonicity in neonatal lambs: resetting of the threshold for vasopressin secretion. 1296 36

Volume and sodium excess is the predominant factor in the pathogenesis of hypertension in dialysis patients. However, except for anephric patients, the relationship between volume status, blood pressure, and hemodynamics is not straightforward, but may vary between subgroups of patients. In general, the sensitivity of blood pressure to changes in the volume/sodium status appears to be increased in patients with end-stage renal disease. The blood pressure response to changes in the sodium/volume status may be influenced by disturbances in the activity of and response to various neurohumoral mechanisms, such as the renin-angiotensin and sympathetic nervous systems, Na-K-ATP-ase inhibitors, and the nitric oxide system. Regarding these aspects, there might be a parallel with salt-sensitive (essential) hypertension. Preliminary data showed a beneficial effect of sodium removal beyond changes in the volume status. Also of interest is the fact that prolonging dialysis time may improve blood pressure control without clear changes in the fluid status. It is hypothesized that a reduction in exchangeable sodium, by increased diffusive transport of sodium, in combination with increased removal of vasopressor substances, might be partly responsible for the observed blood pressure changes during long dialysis times. In conclusion, sodium and volume overload and neurohumoral factors coincide in the pathogenesis of hypertension in dialysis patients. Nevertheless, their exact relationship has not yet been elucidated and deserves further study.
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PMID:Role of sodium and volume in the pathogenesis of hypertension in dialysis patients. Reflections on pathophysiological mechanisms. 1473 12


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