Involvement of the renal kallikrein-kinin system in furosemide-induced natriuresis in rats

This study examined whether the renal kallikrein-kinin system (KKS) is invo lved with furosemide-induced natriuresis in rats. Intravenous administratio n of furosemide (10 mg/kg) to anesthetized rats infused with physiological saline (saline) increased renal KK excretion as well as urine volume and ur inary excretions of sodium, chloride and potassium. The change in the incre ase of renal KK excretion by furosemide at a dose of 1.0 mg/kg relative to the control was larger than that of urine volume. Pretreatment with a Bz-re ceptor antagonist, 8-[3-[N-[(E)-(6-acetamidopyridin-3-yl)acryloylglycyl]-N- methylamino]-2,6-dichlorobenzyloxy] -2-methylquinoline (FR173657, 100 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, urin ary excretion of sodium collected during the first 8 h in metabolic cages s ignificantly reduced by 22.4% when FR173657 (100 mg/kg) was given concurren tly with furosemide (100 mg/kg) and hypotonic saline (5% of body wt.). Thes e results indicate that furosemide increased renal KK excretion through a m echanism 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.