Endothelium-dependent vasodilation by LP-805, a novel vasodilating agent, on rat thoracic aorta

Gen Pharmacol. 1992 May;23(3):343-6. doi: 10.1016/0306-3623(92)90093-y.

Abstract

1. In rat aortae with [E(+)-tissue] and without [E(-)-tissue] intact endothelium, LP-805 relaxed the preparations precontracted with 35.9 mM K+ and its action in E(+)-tissues was more potent than that in E(-)-tissues. Moreover, the inhibitory action of glibenclamide in E(-)-tissues was more potent than that in E(+)-tissues. 2. The relaxing action of LP-805 on E(+)-tissues treated with NG-nitro-L-arginine methyl ester (10 microM), a potent inhibitor of nitric oxide synthesis, was the same as that in E(-)-tissues. 3. Methylene blue (10 microM) also inhibited the LP-805 induced relaxation in E(+)-tissues. 4. Indomethacin (10 microM) had no effect on LP-805-induced relaxation in E(+)-tissues. 5. These results suggest that the vasorelaxant action of LP-805 involves the mechanism which causes the release of nitric oxide (NO) from vascular endothelium.

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiology
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Endothelium, Vascular / physiology*
  • Glyburide / pharmacology
  • In Vitro Techniques
  • Male
  • NG-Nitroarginine Methyl Ester
  • Potassium Channels / drug effects
  • Pyrazoles / pharmacology*
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology*

Substances

  • Potassium Channels
  • Pyrazoles
  • Pyrimidines
  • Vasodilator Agents
  • 8-tert-butyl-6,7-dihydropyrrolo(3,2-e)-5-methylpyrazolo(1,5-a)pyrimidine-3-carbonitrile
  • Arginine
  • Glyburide
  • NG-Nitroarginine Methyl Ester