Prostaglandin reabsorption

There is an additional layer of complexity associated with the effects of renal prostaglandins. In contrast to the medullary enzyme, cortical COX-2 expression is increased by low salt intake, leading to increased renin release. This elevates glomerular filtration rate and contributes to enhanced sodium reabsorption and a rise in blood pressure. PGE2 is thought to stimulate renin release through activation of EP4 or EP2. PGI2 can also stimulate renin release and this may be relevant to maintenance of blood pressure in... 

NSAIDs inhibit prostaglandin synthesis. This can potentiate the effect of water reabsorption in the renal tubules of vasopressin. 

The renal toxicity associated with aldesleukin is dose-related. It manifests as uremia, oliguria, fluid retention, and pronounced renal tubular sodium reabsorption (77). No evidence of tubular dysfunction has been found. There is reduced renal plasma flow associated with reduced renal prostaglandin synthesis and increased plasma renin activity, which may explain the mechanism (84). 

Strandhoy JW, Ott CE, Schneider EG et al. Effects of prostaglandins El and E2 on renal sodium reabsorption and Starling forces. American Journal of Physiology 1974 226 1015-1021. 

About 5% of the filtered lithium may be actively reabsorbed in the thick ascending limb [19]. This active "reabsorption" can increase to about 15% after prostaglandin inhibition [9, 17]. These observations suggest that lithium clearance cannot be used as a precise marker of proximal fluid reabsorption. 

BoerWH, Fransen R, Boer P, Roos R de, Koomans HA. Prostaglandin synthesis inhibition stimulates lithium reabsorption in Henle s loop in rats. Kidney Int 1993 43 301-306. 

MOA Inhibit prostaglandin synthesis by decreasing activity of cyclo-oxygenase Decreases the deposition of urate crystals in joints by decreasing leukocyte motility Decreases the motility of PMN leukocytes Competitive inhibition of uric acid reabsorption at the proximal tubule Inhibits xanthine oxidase, thus preventing uric acid production... 

As a consequence of the blockade of the Na, K, 2Cr-cotransporter, the diuresis produced by furosemide (frusemide) results in increased urinary excretion of sodium, potassium, chloride, calcium and magnesium ions. The losses of sodium, potassium and chloride are approximately 1750, 600 and 2150 mmol, respectively, after i.m. administration of furosemide (frusemide) at 1 mg/kg. Although these electrolyte losses are substantial, they are largely replaced (within the 24 h period following furosemide (frusemide) administration) by enhanced renal reabsorption as well increased ion absorption from the intestinal tract. In addition to this primary action, furosemide (frusemide) may have a lesser inhibitory effect on other chloride ion transporters and the drug can also inhibit carbonic anhydrase activity (Martinez-Maldonado Cordova 1990, Rose 1989,1991, Wilcox 1991). Finally, some of the renal and extrarenal effects of furosemide (frusemide) appear to be mediated through increased prostaglandin production. 

Many drugs and other chemicals can adversely affect renal function by directly or indirectly affecting the reabsorption of electrolytes and water in the kidney. Chlorpropamide can enhance the secretion of ADH and promote the water conservation actions of the hormone, while lithium use can lead to a nephrogenic diabetes insipidus. NSAIDs block the formation of renal prostaglandins, which can result in hyperkalemia. Hyperkalemia may also result from the use of beta blockers, potassium-sparing diuretics, and cyclosporine. 

Bidirectional transport of hydrophobic anions such as methotrexate and folic acid in the brush-border membranes is mediated by 0AT-K1 (7) 0AT-K2 (8) may also participate in tubular reabsorption and/or secretion of hydrophobic anions such as bile acids, methotrexate, and prostaglandin E. MRP2/cM0AT (9) may contribute to tubular secretion of anionic conjugates of hydrophobic compounds. Adapted from [29]. 

The renal saluretic response to loop diuretics is partially dependent on intact intrarenal prostaglandin production in the thick ascending loop of Henle. The decrease in the response to loop diuretics is mediated both by removing the inhibition of sodium chloride reabsorption and an increase in renal medullary blood flow causing a reduction in renal concentrating capacity. The net result is that the concurrent use of a NSAID may blunt the diuresis induced by loop diuretics. 

By extracting water from intracellular compartments, osmotic diuretics expand the extracellular fluid volume, decrease blood viscosity, and inhibit renin release. These effects increase RBF, and the increase in renal medullary blood flow removes NaCl and urea from the renal medulla, thus reducing medullary tonicity. Under some circumstances, prostaglandins may contribute to the renal vasodilation and medullary washout induced by osmotic diuretics. A reduction in medullary tonicity causes a decrease in the extraction of water from the DTL, which limits the concentration of NaCl in the tubular fluid entering the ATL. This latter effect diminishes the passive reabsorption of NaCl in the ATL. In addition, osmotic diuretics may also interfere with transport processes in the TAL. 

While case reports describe the effectiveness of indomethacin in the treatment of nephrogenic DI, other cyclooxygenase inhibitors (e.g., ibuprofen) appear to be less effective. The mechanism of the effect may involve a decrease in glomerular filtration rate, an increase in medullary solute concentration, and/or enhanced proximal reabsorption of fluid. Also, since prostaglandins attenuate vasopressin-induced antidiuresis in patients with at least a partially intact V -receptor system, some of the antidiuretic response to indomethacin may be due to diminution of the prostaglandin effect and enhancement of the effects of vasopressin on principal cells of the collecting duct. 

Fulgraff, G. and Meiforth, A. (1971). Effects of prostaglandin E2 on excretion and reabsorption of sodium and fluid in rat kidneys (micropuncture studies). Pflugers Arch., 330, 243-56... 

Gill, J.R. and Bartter, F.C. (1978). Evidence for a prostaglandin-independent defect in chloride reabsorption in the loop of Henle as a proximal cause of Bartter s syndrome. Am. ]. Med., 65, 766-72... 

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