Jpn. J. Pharmacol. 84 (2), 133-139 (2000)

Involvement of the Renal Kallikrein-Kinin System in Furosemide-Induced Natriuresis in Rats

Tomoe Fujita*, Yuji Kumagai, Yasuhiro Ikeda, Naoya Inamura, Tomonori Iwata, Michiko Ogino and Masataka Majima

Department of Pharmacology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara-shi, Kanagawa 228-8555, Japan
*Corresponding author.ﾊﾊFAX:+81-42-778-8441
E-mail: twata@med.kitasato-u.ac.jp

Abstract: This study examined whether the renal kallikrein-kinin system (KKS) is involved with furosemide-induced natriuresis in rats. Intravenous administration of furosemide (10ﾊmg/kg) to anesthetized rats infused with physiological saline (saline) increased renal KK excretion as well as urine volume and urinary excretions of sodium, chloride and potassium. The change in the increase of renal KK excretion by furosemide at a dose of 1.0ﾊmg/kg relative to the control was larger than that of urine volume. Pretreatment with a B₂-receptor antagonist, 8-[3-[N-[(E)-3-(6-acetamidopyridin-3-yl)acryloylglycyl]-N-methylamino]-2,6-dichlorobenzyloxy]-2-methylquinoline (FR173657, 100ﾊmg/kg), significantly inhibited the furosemide-induced natriuresis by 58.6%. The effect of FR173657 on the furosemide-induced natriuresis was also examined in hypotonic saline-loading rats. Similar to the saline-loading rats, urinary excretion of sodium collected during the first 8ﾊh in metabolic cages significantly reduced by 22.4% when FR173657 (100ﾊmg/kg) was given concurrently with furosemide (100ﾊmg/kg) and hypotonic saline (5% of body wt.). These results indicate that furosemide increased renal KK excretion through a mechanism different from a washout mechanism and induced natriuresis partly through an augmentation of the renal KKS following the increase in renal KK excretion in both the saline- and hypotonic saline-loading rats.

Keywords: B₂-receptor antagonist, FR173657, Furosemide, Natriuresis, Renal kallikrein