Effects of FK409, a novel nitric oxide donor, on renal hemodynamic and excretory responses in anesthetized rat

• Published in: Japanese Journal of Pharmacology 1996, Vol.71 (suppl.2), p.323-323
• Main Authors: Urabe, Kazunori, Matsumura, Yasuo, Nishinra, Manabu, Maeda, Kohsuke, Morimoto, Shiro
• Format: Article
• Language: eng ; jpn
• ISSN: 0021-5198
• DOI: 10.1016/S0021-5198(19)37533-X

The effects of FK409 on renal hemodynamic and excretory responses was investigated in anesthetized rats. FK409 infused into the renal artery at 10 μg/kg/min, caused reduction in mean arterial pressure and increase in renal blood flow. Simultaneously, significant increases in urine flow, urinary excretion of sodium and fractional excretion of sodium were observed. In addition, there was a significant increase in urinary excretion of NO metabolites. In hypertensive rats with impairment of NO formation (treated with NO synthase inhibitor, N^G -nitro-L-arginine, NOARG), FK409 produced remarkable renal vasodilation and diuresis, both of which were significant greater than those in normal rats. In deoxycorticosterone acetate (DOCA)-salt hypertensive rats, FK409 caused a reduction in mean arterial pressure comparable to that seen with normal rats. Renal vasorelaxation induced by FK409 was much less potent than that in normal rats. Intrarenal administration of NOARG to DOCA-salt hypertensive rats caused a potent renal vasoconstriction. Potencies of these responses were similar to those in normal rats. These results indicate that FK409 donates NO, which results in renal vasodilation and diuresis, and that the impairment of basal NO formation leads to enhance the renal responses to FK409 in rat kidney. In addition, in DOCA-salt hypertensive rats, decreased response of renal vasculature to FK409 was not due to abnormal NO generation, but to reduction of response to exogenously applied NO.