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

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.