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.