Renal hemodynamic and excretory responses in anesthetized rats to FK409, a novel nitric oxide donor.
Renal hemodynamic and excretory responses to (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409), a novel nitric oxide (NO) donor, were examined using anesthetized rats. When FK409 was infused into the renal artery of normal rats at 10 micrograms/kg per min, a moderate renal vasodilating effect was observed with a decrease in mean arterial blood pressure. Urine flow, urinary excretion of sodium and fractional excretion of sodium significantly increased by about 85%, 110% and 75%, respectively, compared with each control value. Simultaneously, urinary excretion of NO metabolites (UNOxV) was markedly increased with the administration of FK409. In hypertensive rats treated with NG-nitro-L-arginine (NOARG), the NO synthase inhibitor, FK409 produced a potent renal vasodilation, although the hypotensive effect of the agent was comparable to that seen in normal rats. In addition, glomerular filtration rate was significantly elevated by the agent. There were marked increases in the excretory responses, i.e., levels of urine flow, urinary excretion of sodium and fractional excretion of sodium were increased to about 3-, 6- and 5-fold of each control value, respectively. The extent of increment of UNOxV was similar to that seen in normal rats. These results clearly indicate that FK409 causes renal vasodilation and diuresis, 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.
Urabe
K
K
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Matsumura
Y
Y
Nishiura
M
M
Maeda
K
K
Morimoto
S
S
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006977:Hypertension, Renal / Q000188:drug therapy / Q000378:metabolism; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D009574:Nitro Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000652:urine; D014665:Vasodilator Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D009574:Nitro Compounds; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; C061872:FK 409; D012964:Sodium