RENAL HEMODYNAMIC AND EXCRETORY RESPONSES IN ANESTHETIZED RATS TO FK409, A NOVEL NITRIC-OXIDE DONOR

Renal hemodynamic and excretory responses to -4-ethyl-2-[(E)-hydroxyim ino]-5-nitro-3-hexenamide (FK409), a novel nitric oxide (NO) donor, we re examined using anesthetized rats. When FK409 was infused into the r enal artery of normal rats at 10 mu g/kg per min, a moderate renal vas odilating effect was observed with a decrease in mean arterial blood p ressure. Urine flow, urinary excretion of sodium and fractional excret ion of sodium significantly increased by about 85%, 110% and 75%, resp ectively, compared with each control value. Simultaneously, urinary ex cretion of NO metabolites (UNOxV) was markedly increased with the admi nistration of FK409. In hypertensive rats treated with N-G-nitro-L-arg inine (NOARG), the NO synthase inhibitor, FK409 produced a potent rena l vasodilation, although the hypotensive effect of the agent was compa rable to that seen in normal rats. In addition, glomerular filtration rate was significantly elevated by the agent. There were marked increa ses in the excretory responses, i.e., levels of urine flow, urinary ex cretion of sodium and fractional excretion of sodium were increased to about 3-, 6- and 5-fold of each control value, respectively. The exte nt of increment of UNOxV was similar to that seen in normal rats. Thes e results clearly indicate that FK409 causes renal vasodilation and di uresis, via NO formation. Renal hemodynamic and excretory responses to the agent are sensitive in NO-depleted conditions. FK409 and related compounds may be useful for the treatment of renal diseases, in cases where the basal NO formation is impaired.