Effect of LP-805, a releaser of endothelium-derived nitric oxide, on systemic vasodilatation in vivo

Abstract

We have investigated relations between hypotensive responses to LP-805, a newly synthesized vasodilator, and the production of nitric oxide (NO), in anesthetized rats. LP-805 (0.1-0.5 mg/kg, i.v.) or acetylcholine (ACh) (0.3-3.0 micrograms/kg, i.v.) caused a dose-dependent transient decrease in diastolic blood pressure. The decrease induced by 0.3 mg/kg LP-805 (i.v.) was partially inhibited by pretreatment with NG-nitro-L-arginine (L-NNA), a specific inhibitor of endothelial NO synthase, but the responses to lower or higher doses of LP-805 (0.1 or 0.5 mg/kg, i.v.) were not affected. The dose-dependent decrease in diastolic blood pressure, caused by LP-805, was not affected by pretreatment with L- or D-arginine. The dose-dependent decrease in diastolic blood pressure caused by ACh was not affected by pretreatment with L-NNA or with L- or D-arginine. The hypotensive response to 20-min infusions of LP-805 (100 micrograms/kg per min) was significantly inhibited by pretreatment with L-NNA (10 mg/kg, i.v.). The half-recovery times (T 1/2) of LP-805 or ACh-induced depressor responses were shortened by pretreatment with L-NNA. They were prolonged by L-arginine, but not by D-arginine. This shortening, by L-NNA, of the half-recovery time after LP-805 or ACh was reversed by L-arginine, but not by D-arginine. The T 1/2 of the LP-805-induced hypotensive response was not affected by pretreatment with indomethacin (1 mg/kg, i.v.). In the presence of L-NNA (10 mg/kg, i.v.), the T 1/2 of the LP-805-induced hypotensive response was not affected by pretreatment with indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)