Effect of 5-(N,N-Dimethyl)-amiloride, a specific inhibitor of Na(+)/H(+) exchanger, on the palmitoyl-L-carnitine-induced mechanical and metabolic derangements in the isolated perfused rat heart

Pharmacology. 1999 Nov;59(5):239-48. doi: 10.1159/000028326.

Abstract

The present study was carried out to determine the effect of 5-(N, N-dimethyl)-amiloride (DMA), a specific inhibitor of the Na(+)/H(+) exchanger, on the cardiac mechanical and metabolic derangements induced by palmitoyl-L-carnitine (PALCAR). Rat hearts were perfused aerobically at a constant flow according to the Langendorff technique, while being paced electrically. PALCAR (5 micromol/l) increased the left-ventricular end-diastolic pressure, decreased the left ventricular developed pressure (i.e. mechanical dysfunction), decreased the tissue level of ATP and increased the tissue level of AMP (i.e. metabolic change). DMA (10 or 20 micromol/l) attenuated the mechanical and metabolic alterations induced by PALCAR in a concentration-dependent way. Nevertheless, DMA (10 or 20 micromol/l) did not affect the mechanical function or energy metabolism in the normal (PALCAR-untreated) heart. These results suggest that inhibition of the Na(+)/H(+) exchanger with DMA is effective in attenuating the PALCAR-induced mechanical and metabolic derangements in the heart.

MeSH terms

  • Amiloride / analogs & derivatives*
  • Amiloride / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Energy Metabolism / drug effects
  • Enzyme Inhibitors / pharmacology*
  • Heart / drug effects*
  • In Vitro Techniques
  • Male
  • Myocardial Contraction / drug effects*
  • Myocardium / metabolism*
  • Palmitoylcarnitine / pharmacology*
  • Perfusion
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Hydrogen Exchangers / antagonists & inhibitors*
  • Ventricular Function, Left / drug effects

Substances

  • Enzyme Inhibitors
  • Sodium-Hydrogen Exchangers
  • Palmitoylcarnitine
  • 5-dimethylamiloride
  • Amiloride