Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In human red cells, Ca is mainly bound to the inner side of the plasma membrane. A smaller part may be present within intracellular Ca storing vesicles, while only a few percent of total red cell Ca is in ionized form. In some hemolytic anemias (sickle cell anemia, beta-thalassemia), an increased number of endocytotic vesicles storing Ca is probably responsible for the elevation of total red cell Ca content. Red cell Ca inward transport, which is partially susceptible to inhibition by Ca entry blockers, has been reported to be enhanced by physiological shear stress and enrichment in membrane cholesterol, as well as in some hemolytic anemias. Normal intracellular ionized Ca levels have been assessed in several diseases where elevated Ca inward transport rates or decreased Ca efflux through the Ca pump (hemolytic anemias, cystic fibrosis, essential hypertension) had been observed previously. Thus, red cell Ca homeostasis is apparently capable of keeping ionized Ca levels within the physiological range of 20-60 nM under most pathological conditions investigated so far. Conceptually, changes in red cell Ca homeostasis (or also in other red cell membrane parameters) may be of pathophysiological importance in two respects: 1) A disturbance may be directly responsible for some of the symptoms associated with a disease. This is the case in sickle cell anemia, where red cell dehydration is possibly caused by transient elevations of intracellular ionized calcium, which may activate K efflux through the Ca-activated K channel. The presence of dehydrated red cells will, in turn, lead to microvascular occlusion, a pathophysiologically important phenomenon in sickle cell anemia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Calcium homeostasis of human erythrocytes and its pathophysiological implications. 164 22

Prostaglandins are currently used to maintain patency of the ductus arteriosus and to elicit uterine contractions. Prostaglandin synthesis inhibitors are used to promote closure of the ductus and their administration in pregnant animals has produced fetal pulmonary hypertension. Exposure of the human fetus to inhibitors of prostaglandin synthesis has been associated with persistent pulmonary hypertension. A case report of a child with primary hypertension supports the hypothesis that the balance of prostaglandin metabolites plays an important role in maintaining PVR. Leukotrienes have been identified in the sputum of allergic asthmatic patients, patients with cystic fibrosis and infants with persistent pulmonary hypertension. Leukotriene inhibition in rats and newborn lambs prevented and reversed HPV. Receptors for prostaglandins have been identified in smooth muscle preparations of the uterus and renal glomerulus. Further studies have characterized the binding sites in lung tissue, giving supportive evidence for the existence of receptor sites there. Specific receptor sites for LTC4 and LTD4 have been demonstrated in lung tissue. Temperature, pH, and the presence of cations and guanine nucleotides have been shown to affect the receptor density and affinity. Lewis et al demonstrated that the characteristics of the receptor for [3H]LTD4 in the human lung are identical in adult and fetal tissue. This leads to the need for further investigation of the receptors and the effects of the local environments in an attempt to explain the physiologic changes seen in the successful and unsuccessful transition from fetal to neonatal circulation.
 ...
PMID:Prostaglandin and leukotriene receptors in pulmonary, vascular, and uterine smooth muscle. 303 20

Findings of increased secretion rate and decreased metabolic clearance rate (MCR) of aldosterone in patients with cystic fibrosis of the pancreas (CF) and our own evidence on the association of increased aldosterone-binding globulin (ABG)-binding and decreased MCR in essential hypertension (EH) inspired us to investigate the plasma aldosterone, with the inclusion of protein-binding variables, in CF patients. (1) The percentage of plasma aldosterone specifically bound to ABG was measured in 55 young adults with CF in addition to total plasma aldosterone, total plasma corticosteroids and for comparison of corticosteroid-binding globulin (CBG)-binding capacity. (2) The percentage of ABG-bound plasma aldosterone was found to vary with the seasonal change in temperature and the hepatic function of CF patients. Many of the CF patients, particularly during spring, summer and fall, had elevated plasma ABG-bound aldosterone which would be expected to result in low MCR. This binding was less elevated during cooler weather, suggesting that ABG-bound aldosterone is participating in the adaptation to warmer weather by probably increasing extrarenal sodium retention, thereby preventing a fall of blood pressure (BP) to pathologically low levels. A significant correlation was consequently found between the ABG capacity and the ambient temperature. (3) CF patients with low liver function had significantly lower protein binding of aldosterone and only slightly lower CGB capacity, presumably due to disturbed protein synthesis by the liver. (4) In some patients, elevated total plasma aldosterone and total corticosteroids were found, probably as a result of an adaptation to excessive sweat losses of sodium and the consequent contraction of intravascular volume. (5) Our findings also demonstrated a positive correlation between plasma ABG-bound aldosterone and both systolic and diastolic BP.
 ...
PMID:The relationship of plasma aldosterone-binding globulin to blood pressure regulation in young adults with cystic fibrosis. 365 2

The epithelial sodium channel (ENaC) is of fundamental importance in the control of sodium fluxes in epithelial cells. Modulation of sodium reabsorption through the distal nephron ENaC is an important component in the overall control of sodium balance, blood volume and thereby of blood pressure. This is clearly demonstrated by rare genetic disorders of sodium-channel activity (Liddle's syndrome and pseudohypoaldosteronism type 1), associated with contrasting effects on blood pressure. The mineralocorticoid aldosterone is a well-established modulator of sodium-channel activity. Considerable insight has now been gained into the intracellular signalling pathways linking aldosterone-mediated changes in gene transcription with changes in ion transport. Activating pathways include aldosterone-induced proteins and especially the serum- and glucocorticoid-inducible kinase (SGK) and the small G-protein, K-Ras 2A. Targeting of the ENaC for endocytosis and degradation is now emerging as a major mechanism for the down-regulation of channel activity. Several proteins acting in concert are an intrinsic part of this process but Nedd4 (neural precursor cell expressed developmentally down-regulated 4) is of central importance. Other mechanisms known to interact with ENaC and affect sodium transport include channel-activating protease 1 (CAP-1), a membrane-anchored protein, and the cystic fibrosis transmembrane regulator. The implications of research on accessory factors controlling ENaC activity are wide-ranging. Understanding cellular mechanisms controlling ENaC activity may provide a more detailed insight not only of ion-channel abnormalities in cystic fibrosis but also of the link between abnormal renal sodium transport and essential hypertension.
 ...
PMID:Regulation of the epithelial sodium channel by accessory proteins. 1246 Jan 20

The amiloride-sensitive epithelial sodium channel (ENaC), a multimeric plasma membrane protein composed of alpha-, beta-, and gamma-ENaC subunits, mediates Na(+) reabsorption in epithelial tissues, including the distal nephron, colon, lung, and secretory glands, and plays a critical role in pathophysiology of essential hypertension and cystic fibrosis (CF). The function of ENaC is tightly regulated by signals elicited by aldosterone, vasopressin, agents that increase intracellular cAMP levels, ions, ion channels, G-protein-coupled mechanisms, and cytoskeletal proteins. In this paper, the effects of Ca(2+) on the expression of the human ENaC subunits expressed in human embryonic kidney cells (HEK-293 cells) were examined. Incubation of cells with increased extracellular Ca(2+) and treatment of cells with A23187 and thapsigargin stimulated the expression of the monomeric ENaC subunits. Treatment of cells with Ca(2+)-chelating agents, EGTA and BAPTA-AM, reduced the levels of ENaC subunit expression. The pulse-chase experiments suggested that a rise in the intracellular Ca(2+) increases the ENaC subunit expression. Immunoblot analysis using the anti-ubiquitin antibody indicated that ENaC undergoes ubiquitination. A correlation between the processes that regulate ENaC function with the intracellular Ca(2+) was discussed.
 ...
PMID:Role of intracellular Ca2+ in the expression of the amiloride-sensitive epithelial sodium channel. 1467 Mar 68

The epithelial sodium channel (ENaC) is composed of three homologous subunits and allows the flow of Na(+) ions across high resistance epithelia, maintaining body salt and water homeostasis. ENaC dependent reabsorption of Na(+) in the kidney tubules regulates extracellular fluid (ECF) volume and blood pressure by modulating osmolarity. In multi-ciliated cells, ENaC is located in cilia and plays an essential role in the regulation of epithelial surface liquid volume necessary for cilial transport of mucus and gametes in the respiratory and reproductive tracts respectively. The subunits that form ENaC (named as alpha, beta, gamma and delta, encoded by genes SCNN1A, SCNN1B, SCNN1G, and SCNN1D) are members of the ENaC/Degenerin superfamily. The earliest appearance of ENaC orthologs is in the genomes of the most ancient vertebrate taxon, Cyclostomata (jawless vertebrates) including lampreys, followed by earliest representatives of Gnathostomata (jawed vertebrates) including cartilaginous sharks. Among Euteleostomi (bony vertebrates), Actinopterygii (ray finned-fishes) branch has lost ENaC genes. Yet, most animals in the Sarcopterygii (lobe-finned fish) branch including Tetrapoda, amphibians and amniotes (lizards, crocodiles, birds, and mammals), have four ENaC paralogs. We compared the sequences of ENaC orthologs from 20 species and established criteria for the identification of ENaC orthologs and paralogs, and their distinction from other members of the ENaC/Degenerin superfamily, especially ASIC family. Differences between ENaCs and ASICs are summarized in view of their physiological functions and tissue distributions. Structural motifs that are conserved throughout vertebrate ENaCs are highlighted. We also present a comparative overview of the genotype-phenotype relationships in inherited diseases associated with ENaC mutations, including multisystem pseudohypoaldosteronism (PHA1B), Liddle syndrome, cystic fibrosis-like disease and essential hypertension.
...
PMID:Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases. 2677 8