Effects of LP-805, a novel vasorelaxant agent, a potassium channel opener, on rat thoracic aorta

Gen Pharmacol. 1992 May;23(3):347-53. doi: 10.1016/0306-3623(92)90094-z.

Abstract

1. In rat thoracic aorta, LP-805 (0.1-10 microM) caused the marked reduction of NE-induced maximum response and relaxed the low K+ (less than 35.9 mM)-induced contraction, in a concentration-dependent manner, but failed to relax the high K+ (65.9 mM)-induced contraction. 2. Glibenclamide (0.3-1 microM) caused a parallel shift of concentration-response curve produced by LP-805 for 25.9 mM K(+)-induced contraction and prevented the LP-805-induced reduction in maximum response evoked by NE in a concentration-dependent manner. 3. Glibenclamide (10 microM) prevented the LP-805 (10 microM)-induced decrease in cytosolic Ca2+ levels which was increased by 1 microM NE or 25.9 mM K+. 4. LP-805 (10 microM) increased basal 86Rb efflux, which was completely inhibited by 10 microM glibenclamide. 5. The results suggest that LP-805 causes a vasorelaxation as a consequence of the decrease in cytosolic Ca2+ levels due to the increase in K+ efflux via opening ATP-dependent K+ channels.

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / metabolism
  • Calcium / metabolism
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Fura-2 / pharmacology
  • Glyburide / pharmacology
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Norepinephrine / pharmacology
  • Potassium / pharmacology
  • Potassium Channels / drug effects*
  • Pyrazoles / pharmacology*
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Rubidium Radioisotopes
  • Vasodilator Agents / pharmacology*

Substances

  • Potassium Channels
  • Pyrazoles
  • Pyrimidines
  • Rubidium Radioisotopes
  • Vasodilator Agents
  • 8-tert-butyl-6,7-dihydropyrrolo(3,2-e)-5-methylpyrazolo(1,5-a)pyrimidine-3-carbonitrile
  • Potassium
  • Glyburide
  • Calcium
  • Fura-2
  • Norepinephrine