Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats.
Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats were observed. Effects of K+ channel modulation on glomerular filtration rate and electrolyte excretion were studied using the adenosine-triphosphate- (ATP)-sensitive K+ channel blocker 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydr ochloride (U-37883A) in conscious rats previously equipped with catheters for clearance studies. In saline-loaded rats, i.v. doses of U-37883A of 1.7, 5.0 and 15 mg/kg increased absolute and fractional Na+ excretion dose-dependently without changing K+ excretion. The glomerular filtration rate remained constant during diuresis. In water-loaded (hypotonic dextrose) rats, free-water clearance studies revealed that the ATP-sensitive K+ channel blocker significantly decreased an index of solute reabsorption (free-water clearance adjusted for chloride clearance) in the diluting segment during peak natriuretic activity. In addition, U-37883A significantly decreased the osmolality of renal papillary interstitial fluid, indicative of an effect in the medullary portion of the diluting segment. Together, these findings suggest that ATP-sensitive K+ channels, possibly those located at the apical boarder, play a pivotal role in Na+ reabsorption in the thick ascending limb of the loop of Henle.
Ludens
J H
JH
Upjohn Laboratories, Kalamazoo, Michigan 49001, USA.
Clark
M A
MA
Lawson
J A
JA
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000378:metabolism*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects*; D009994:Osmolar Concentration; D026902:Potassium Channel Blockers; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water / Q000008:administration & dosage
D004232:Diuretics; D004573:Electrolytes; D009025:Morpholines; D026902:Potassium Channel Blockers; D014867:Water; C082658:U 37883A; D000218:Adamantane