Ethacrynic acid and furosemide alter Cl, K, and Na distribution between blood, choroid plexus, CSF, and brain.
Can loop diuretics like ethacrynic acid and furosemide, when administered intravenously, significantly alter ion transport and fluid dynamics in CNS? To shed light on this unresolved issue, we tested the ability of these agents to effect redistribution of Na, K and Cl in adult rat brain. Cl penetration into various CNS regions was assessed as the volume of distribution, i.e., uptake, of 36Cl from blood. Ethacrynic acid and furosemide (50 mg/kg IV) reduced by 20-30% the rate of permeation of 36Cl across the blood-CSF barrier, and they elevated [K] and [Cl] in choroid plexus (CP) by 15-25%. The loop diuretic-induced buildup of K and Cl in CP (lateral and 4th ventricle) was likely a reflection of decreased movement of these ions across the apical membrane into CSF. 36Cl activity in parietal cortex and pons-medulla decreased in treatment with furosemide and ethacrynic acid, due to slowing of Cl transport across blood-brain and/or blood-CSF barriers. Our inhibitory findings in intact rats are consistent with those from previous in vitro experiments demonstrating diminution by loop diuretics of Na, K and Cl transport across isolated CP membranes.
Johanson
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CE
Department of Clinical Neurosciences, Brown University/Rhode Island Hospital, Providence 02902.
Murphy
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VA
Dyas
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D000086:Acetazolamide / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D002712:Chlorides / Q000378:metabolism; D002831:Choroid Plexus / Q000187:drug effects* / Q000378:metabolism; D004573:Electrolytes / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects; D010313:Partial Pressure; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism
D002712:Chlorides; D004573:Electrolytes; D002245:Carbon Dioxide; D000584:Amiloride; D005665:Furosemide; D012964:Sodium; D004976:Ethacrynic Acid; D000086:Acetazolamide; D011188:Potassium