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10.1371/journal.pone.0079327 http://scihub22266oqcxt.onion/10.1371/journal.pone.0079327 24260196!3832474!24260196     free     free     free Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       PLoS+One 2013 ; 8 (11): e79327 Nephropedia Template TP {{tp|p=24260196|t=2013. Potentiation of the effect of thiazide derivatives by carbonic anhydrase inhibitors: molecular mechanisms and potential clinical implications |pdf=|usr=}}{{24260196}} gab.com Text Potentiation of the effect of thiazide derivatives by carbonic anhydrase inhibitors: molecular mechanisms and potential clinical implications JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=24260196 #FOAvip BACKGROUND: Carbonic anhydrase inhibitors (CAI) are mild diuretics, hence not widely used in fluid overloaded states. They are however the treatment of choice for certain non-kidney conditions. Thiazides, specific inhibitors of Na-Cl cotransport (NCC), are mild agents and the most widely used diuretics in the world for control of mild hypertension. HYPOTHESIS: In addition to inhibiting the salt reabsorption in the proximal tubule, CAIs down-regulate pendrin, therefore leaving NCC as the major salt absorbing transporter in the distal nephron, and hence allowing for massive diuresis by the inhibitors of NCC in the setting of increased delivery of salt from the proximal tubule. EXPERIMENTAL PROTOCOLS AND RESULTS: Daily treatment of rats with acetazolamide (ACTZ), a known CAI, for 10 days caused mild diuresis whereas daily treatment with hydrochlorothiazide (HCTZ) for 4 days caused hardly any diuresis. However, treatment of rats that were pretreated with ACTZ for 6 days with a combination of ACTZ plus HCTZ for 4 additional days increased the urine output by greater than 2 fold (p<0.001, n = 5) compared to ACTZ-treated animals. Sodium excretion increased by 80% in the ACTZ plus HCTZ group and animals developed significant volume depletion, metabolic alkalosis and pre-renal failure. Molecular studies demonstrated approximately 75% reduction in pendrin expression by ACTZ. The increased urine output in ACTZ/HCTZ treated rats was associated with a significant reduction in urine osmolality and reduced membrane localization of AQP-2 (aquaporin2). CONCLUSIONS: These results indicate that ACTZ down-regulates pendrin expression and leaves NCC as the major salt absorbing transporter in the distal nephron in the setting of increased delivery of salt from the proximal tubule. Despite being considered mild agents individually, we propose that the combination of ACTZ and HCTZ is a powerful diuretic regimen. Twit Text FOAVip Potentiation of the effect of thiazide derivatives by carbonic anhydrase inhibitors: molecular mechanisms and potential clinical implications ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=24260196 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24260196 #FOAvip English Wikipedia <ref>{{Cite pmid|24260196}}</ref> Potentiation of the effect of thiazide derivatives by carbonic anhydrase inhibitors: molecular mechanisms and potential clinical implications #MMPMID24260196 Zahedi K; Barone S; Xu J; Soleimani M PLoS One 2013[]; 8 (11): e79327 PMID24260196show ga BACKGROUND: Carbonic anhydrase inhibitors (CAI) are mild diuretics, hence not widely used in fluid overloaded states. They are however the treatment of choice for certain non-kidney conditions. Thiazides, specific inhibitors of Na-Cl cotransport (NCC), are mild agents and the most widely used diuretics in the world for control of mild hypertension. HYPOTHESIS: In addition to inhibiting the salt reabsorption in the proximal tubule, CAIs down-regulate pendrin, therefore leaving NCC as the major salt absorbing transporter in the distal nephron, and hence allowing for massive diuresis by the inhibitors of NCC in the setting of increased delivery of salt from the proximal tubule. EXPERIMENTAL PROTOCOLS AND RESULTS: Daily treatment of rats with acetazolamide (ACTZ), a known CAI, for 10 days caused mild diuresis whereas daily treatment with hydrochlorothiazide (HCTZ) for 4 days caused hardly any diuresis. However, treatment of rats that were pretreated with ACTZ for 6 days with a combination of ACTZ plus HCTZ for 4 additional days increased the urine output by greater than 2 fold (p<0.001, n = 5) compared to ACTZ-treated animals. Sodium excretion increased by 80% in the ACTZ plus HCTZ group and animals developed significant volume depletion, metabolic alkalosis and pre-renal failure. Molecular studies demonstrated approximately 75% reduction in pendrin expression by ACTZ. The increased urine output in ACTZ/HCTZ treated rats was associated with a significant reduction in urine osmolality and reduced membrane localization of AQP-2 (aquaporin2). CONCLUSIONS: These results indicate that ACTZ down-regulates pendrin expression and leaves NCC as the major salt absorbing transporter in the distal nephron in the setting of increased delivery of salt from the proximal tubule. Despite being considered mild agents individually, we propose that the combination of ACTZ and HCTZ is a powerful diuretic regimen. |Acetazolamide/pharmacology[MESH] |Animals[MESH] |Carbonic Anhydrase Inhibitors/*pharmacology[MESH] |Chloride-Bicarbonate Antiporters/metabolism[MESH] |Diuretics/*pharmacology[MESH] |Kidney/*drug effects/*metabolism[MESH] |Nephrons/drug effects[MESH] |Rats[MESH] |Rats, Sprague-Dawley[MESH] |Sodium Chloride Symporters/metabolism[MESH] |Sulfate Transporters[MESH]Potentiation of the effect of thiazide derivatives by carbonic anhydra(epmc).pdf DeepDyve Pubget Overpricing