Laboratory Investigation

Kidney International (1983) 24, 58–65; doi:10.1038/ki.1983.126

Regulation of kallikrein and renin release by the isolated perfused rat kidney

Jiro Misumi1, François Alhenc-Gelas1, Michel Marre1, Jeanine Marchetti1, Pierre Corvol1 and Joel Menard1

1Institut National de la Santé et de la Recherche Medicale, Unite 36, Paris, France

Correspondence: Dr J Misumi, INSERM U36 - 17, Rue du Fer a Moulin, 75005 Paris, France

Received 1 September 1982; Revised 30 December 1982.

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Abstract

Regulation of kallikrein and renin release by the isolated perfused rat kidney. Rat kidneys perfused in vitro released kallikrein in urine, and renin and kallikrein in the perfusate. The kallikrein was characterized by its kininogenase activity and released bradykinin from bovine and dog substrates. Inactive trypsin activatable kallikrein was present in both perfusate and urine. Kallikrein secretion in urine was influenced by changes in perfusion pressure (PP). Raising the PP strikingly increased urinary kallikrein and lowering PP reduced it. Urinary water and electrolyte output were augmented to the same extent by furosemide and mannitol administration as by raising the PP, but neither drug affected kallikrein. Isoproterenol stimulated the release of renin but not kallikrein. Stopping the oxygen supply to the perfusate suppressed kallikrein secretion in urine and renin release in the perfusate. The kidneys released ten times less kallikrein in the perfusate than in urine, and perfusate kallikrein was not influenced by changes in PP. It is concluded that in this model, changes in PP and/or renal blood flow and/or oxygen supply regulate kallikrein secretion in urine, but that this secretion is unaffected by changes in urinary output. We also conclude that kallikrein release in urine and renin release in perfusate are regulated simultaneously by renal hemodynamic changes but are not affected concomitant by beta-adrenergic stimulation or changes in distal urine composition.

Régulation de la sécrétion de kallicréine et de rénine par le rein de rat isolé perfusé. Le rein de rat isolé perfusé sécrète de la kallicréine dans l'urine, de la rénine et de la kallicréine dans le perfusat. La kallicréine rénale libère de la bradykinine par l'hydrolyse du kininogène de boeuf et de chien. L'activité kallicréine est quantifiée par la mesure de la bradykinine formée. On retrouve de la kallicréine inactive, activable par la trypsine, dans le perfusat et dans l'urine. La sécrétion de kallicréine dans l'urine est régulée par les changements de pression de perfusion (PP) du rein. Une augmentation de PP stimule puissamment la libération de kallicréine et une diminution de PP réduit cette libération. Le furosémide et le mannitol produisent la même augmentation de diurèse que l'augmentation de PP, mais n'influencent pas la sécrétion de kallicréine. L'isoprotérénol stimule la libération de rénine, mais pas celle de kallicréine. L'arrêt de l'apport d'oxygène dans le perfusat supprime la sécrétion de kallicréine dans l'urine et celle de rénine dans le perfusat. Le rein libère dix fois moins de kallicréine dans le perfusat que dans l'urine. La libération de kallicréine dans le perfusat n'est pas influencée par les changements de PP. En conclusion, les changements de PP et/ou de débit sanguin rénal et/ou d'apport en oxygène régulent la sécrétion urinaire de kallicréine par le rein perfusé isolé. Les variations de volume et de composition de l'urine sont sans effets sur cette sécrétion. Par ailleurs, la sécrétion de kallicréine dans l'urine et celle de rénine dans le perfusat sont régulées simultanément lors des changements de l'hemodynamique intrarénale mais pas lors d'une stimulation beta-adrénergique ou lors des changements de composition de l'urine distale qui influencent la rénine mais pas la kallicréine.

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