RT Journal Article
SR Electronic
T1 Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1375
OP 1381
VO 273
IS 3
A1 Ludens, J H
A1 Clark, M A
A1 Lawson, J A
YR 1995
UL http://jpet.aspetjournals.org/content/273/3/1375.abstract
AB 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.