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

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  • Fujita Tomoe
    Department of Pharmacology,Kitasato University School of Medicine,1-15-1 Kitasato,Sagamihara-shi,Kanagawa 228-8555,Japan
  • Kumagai Yuji
    Department of Pharmacology,Kitasato University School of Medicine,1-15-1 Kitasato,Sagamihara-shi,Kanagawa 228-8555,Japan
  • Ikeda Yasuhiro
    Department of Pharmacology,Kitasato University School of Medicine,1-15-1 Kitasato,Sagamihara-shi,Kanagawa 228-8555,Japan
  • Inamura Naoya
    Department of Pharmacology,Kitasato University School of Medicine,1-15-1 Kitasato,Sagamihara-shi,Kanagawa 228-8555,Japan
  • Iwata Tomonori
    Department of Pharmacology,Kitasato University School of Medicine,1-15-1 Kitasato,Sagamihara-shi,Kanagawa 228-8555,Japan
  • Ogino Michiko
    Department of Pharmacology,Kitasato University School of Medicine,1-15-1 Kitasato,Sagamihara-shi,Kanagawa 228-8555,Japan
  • Majima Masataka
    Department of Pharmacology,Kitasato University School of Medicine,1-15-1 Kitasato,Sagamihara-shi,Kanagawa 228-8555,Japan

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Abstract

This study examined whether the renal kallikrein−kinin system(KKS)is involved with furosemide−induced natriuresis in rats.Intravenous administration of furosemide(10 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 1.0mg/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−dichloro−benzyloxy]−2−methylquinoline(FR173657, 100mg/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 h in metabolic cages significantly reduced by 22.4% when FR173657(100mg/kg)was given concurrently with furosemide(100mg/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.

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