Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats

J Pharmacol Exp Ther. 1995 Jun;273(3):1375-81.

Abstract

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.

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / pharmacology
  • Animals
  • Diuretics / pharmacology*
  • Dose-Response Relationship, Drug
  • Electrolytes / metabolism*
  • Glomerular Filtration Rate / drug effects*
  • Male
  • Morpholines / pharmacology*
  • Natriuresis / drug effects*
  • Osmolar Concentration
  • Potassium Channel Blockers*
  • Rats
  • Rats, Sprague-Dawley
  • Water / administration & dosage

Substances

  • Diuretics
  • Electrolytes
  • Morpholines
  • Potassium Channel Blockers
  • Water
  • U 37883A
  • Adamantane