Disease relevance of furosemide

• Fluid secretion in the nephron: Relation to renal failure [1].
• Disorders of distal nephron function, such as Gitelman's syndrome, nephrolithiasis, and adaptation to diuretic drug administration, emphasize the importance of this relatively short nephron segment to human physiology [2].
• We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis [3].
• In patients with chronic renal insufficiency who are undergoing cardiac angiography, hydration with 0.45 percent saline provides better protection against acute decreases in renal function induced by radiocontrast agents than does hydration with 0.45 percent saline plus mannitol or furosemide [4].
• Promotion of patent ductus arteriosus by furosemide [5].

Psychiatry related information on furosemide

• Furosemide and related agents might be useful as neuroprotective agents in alcohol abuse [6].
• Rats were made: (1) diuretic by giving them sugar water (with or without food) or furosemide; or (2) antidiuretic by water deprivation [7].
• METHODS: Transit in the stomach, the small intestine, and the large intestine was assessed concurrently using a wholly scintigraphic technique; psychological status was assessed using established psychometric measures [8].
• We tested the hypothesis that low nephron number is already present during fetal development, and the expression pattern of important molecules of the IGF system is altered in MWF rat during the critical period of kidney development [9].
• For patients severely affected by pain and narcotic dependence with this syndrome, renal autotransplantation may provide a nephron-sparing surgical solution [10].

High impact information on furosemide

• Vacuolar H(+)-ATPases are expressed in the plasma membrane in the kidney almost along the entire length of the nephron with apical and/or basolateral localization patterns [11].
• These go through the intricate process of mesenchyme-to-epithelium transition by which epithelial cell polarization is initiated, and they continue to differentiate into the highly specialized epithelial cell populations of the nephron [12].
• Because the terminal nephron segments, including the DCT and collecting tubule, reabsorb only a small portion of the filtered Mg (approximately 5%), the loop of Henle plays a major role in the determination of Mg reabsorption, and it is in this segment that the major regulatory factors act to maintain Mg balance [13].
• Ion transport mechanisms in thick ascending limb of Henle's loop of mammalian nephron [14].
• The marked increases in glomerular filtration rate and nephron blood flow, which occur at least in some conditions, increase the absolute amount of water and solute delivered to the various nephron segments in ultrafiltrate and peritubular blood [15].

Chemical compound and disease context of furosemide

• During the study, the incidence of patent ductus arteriosus was significantly higher (P less than 0.02) in the furosemide group (18 of 33 infants) than in the chlorothiazide group (8 of 33) [16].
• We conclude that furosemide increases the incidence of patent ductus arteriosus in premature infants with the respiratory-distress syndrome, probably through a prostaglandin-mediated process [16].
• To determine if aldosterone, one of the principal regulators of urinary Na reabsorption by the distal nephron, affects prostasin expression, we examined prostasin mRNA and protein in a cultured mouse cortical collecting duct cell line (M-1), whole rats, and patients with primary aldosteronism [17].
• Correction of hypokalemia and maintenance of a normal serum potassium decreased intracellular [Na+] to 8.2 +/- 1.8 mmol/liter cells, a normal value, and corrected the ouabain-sensitive and furosemide-sensitive 22Na effluxes [18].
• The lowering effect of indomethacin on plasma renin activity is not specifically related to hemorrhage because it also prevented the increase in plasma renin activity elicited by 5 mg/kg of furosemide [19].

Biological context of furosemide

• Furthermore, the decrease of furosemide-stimulated plasma renin activity suggests that alterations of the renin-angiotensin system may help lower blood pressure in certain patients [20].
• This then undergoes morphogenesis and is transformed into the excretory system of the kidney, the nephron [21].
• In this nephron segment, vasopressin regulates water permeability by endo- and exocytosis of water channels from or to the apical membrane [22].
• Both proteins localize to the distal nephron, a kidney segment involved in salt, K+, and pH homeostasis [23].
• Adrenergic mediated signal transduction has been examined in some nephron segments, but virtually nothing is known about the relationship between the generation of adrenoceptor-mediated second messengers and changes in phosphorylation/activity of transport proteins (ion channels, ion pumps) in different types of renal tubular cells [24].

Anatomical context of furosemide

• The apparent marked capacity for compensatory growth in all nephron segments and even in portions of tubular segments in parenchymal renal disease increases the area for transport by tubular epithelia in residual nephrons, as the overall number of nephrons diminishes.. [15].
• The high deformability of erythrocytes which is essential for their transport through the capillaries depends critically on their discoid shape and on the elasticity of the plasma membrane, which may be determined by interactions of the cytoskeleton, the lipid/protein leaflet and the glycocalyx [25].
• Thus, Wnt-4 appears to act as an autoinducer of the mesenchyme to epithelial transition that underlies nephron development [21].
• Images of the intrinsic optical signal acquired during these slice experiments indicated that furosemide coincidentally blocked changes in extracellular space [26].
• The kidney can be thought of as the pairing of two tubes: an epithelial tube (the nephron), carrying filtered blood and engaged in ion and water transport; and endothelial tubes (the blood vessels), delivering blood and carrying away recovered solute [27].

Associations of furosemide with other chemical compounds

• Treated patients exhibited significant (P less than 0.05) reductions of blood pressure when supine and upright, and of plasma dopamine-beta-hydroxylase activity, and furosemide-stimulated renin activity when upright [20].
• In a double-blind, randomized, crossover study, we compared the effect of an aerosol of the loop diuretic furosemide with that of a placebo on the early (within 60 minutes) and late (4 to 12 hours) asthmatic responses to a specific inhaled allergen [28].
• Both hydrochlorothiazide and furosemide significantly reduced blood pressure (BP) during three months of therapy [29].
• Using a targeted proteomics approach, we screened renal protein extracts with rabbit polyclonal antibodies directed to each of the major Na transporters expressed along the nephron to determine whether escape from aldosterone-mediated Na retention is associated with decreased abundance of one or more of renal Na transporters [30].
• Angiotensin II binding sites in individual segments of the rat nephron [31].

Gene context of furosemide

• Pharmacologic inhibition of AngII prevented TGF-alpha and TACE accumulation as well as renal lesions after nephron reduction [32].
• While CFTR is expressed along the entire nephron, its function in renal tubule epithelial cells remains unclear, as no specific renal phenotype has been identified in cystic fibrosis [33].
• Thus, the two AVP receptor subtypes are distributed differently along the nephron, and these mRNAs are regulated differently in the dehydrated state [34].
• While macro- and microscopic kidney development appear to proceed normally in mice that lack Foxi1, electron microscopy reveals an altered ultrastructure of cells lining the distal nephron [35].
• We showed previously that AP-1 complexes are activated during the proliferative response that parallels the development of renal lesions after nephron reduction, but little is known about the specific role of individual Jun/Fos components in the deterioration process [36].

Analytical, diagnostic and therapeutic context of furosemide

• These data show that human D is catabolized by the kidney via glomerular filtration and reabsorption by the proximal nephron [37].
• To assess the renal functional adaptation to reduced excretory capacity, we studied whole kidney and single nephron function in anesthetized volume-replete rabbits after unilateral (left kidney) nephrectomy (UNX), ureteral obstruction (UO), or ureteroperitoneostomy (UP) [38].
• Acute papillectomy or furosemide perfusion was performed to interrupt distal tubular fluid flow past the macula densa, thus minimizing tubuloglomerular feedback-dependent influences on afferent arteriolar function [39].
• Micropuncture during the nonhypertensive period revealed increases in afferent (65%) and efferent (82%) arteriolar resistances, thereby reducing nephron plasma flow rate [40].
• HEK/EP1 [Ca2+]i responses were observed mainly in preparations from rabbits on a low-salt diet and were completely inhibited by either a selective COX-2 inhibitor or an EP1 antagonist, and also by 100 microM luminal furosemide [41].

References