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.
Kishii
K
K
POLA Pharmaceutial R&D Laboratory, Yokohama, Japan.
Morimoto
T
T
Nakajima
N
N
Tsujitani
M
M
Takayanagi
I
I
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D015221:Potassium Channels / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D011720:Pyrazoles; D011743:Pyrimidines; D014665:Vasodilator Agents; C073993:8-tert-butyl-6,7-dihydropyrrolo(3,2-e)-5-methylpyrazolo(1,5-a)pyrimidine-3-carbonitrile; D001120:Arginine; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester