Involvement of renal kallikrein in the regulation of bicarbonate excretion in rats.
1. The experiments reported here were performed to test the hypothesis that renal kallikrein is involved in the regulation of acid-base balance. 2. The bicarbonate concentration and the kallikrein activity in the spontaneously voided urine of conscious rats (experiment 1) were inversely correlated (correlation coefficient (r) = -0.63, P < 0.0001). The correlation was even greater when the urinary bicarbonate concentration was expressed per milligram excreted creatinine (r = -0.74, P < 0.00002). 3. Intravenous injection of the kallikrein inhibitor aprotinin in barbiturate-anaesthetized rats (experiment 2) reduced urinary kallikrein activity (P < 0.05) and increased bicarbonate excretion rate (P < 0.012). 4. Renal arterial infusion of aprotinin in barbiturate-anaesthetized rats (experiment 3) reduced urinary kallikrein activity (120 min, P < 0.01), and increased bicarbonate excretion rate (120 min, P < 0.01). Animals infused with the inhibitor developed a moderate metabolic acidosis (base excess: control, 2.9 +/- 0.7 mM (mean +/- S.E.M.); experimental, -8.1 +/- 0.7 mM; P < 0.05). 5. The bicarbonate concentration of urine fractions obtained after retrograde injection of kallikrein through the ureter into the collecting duct system of barbiturate-anaesthetized rats was lower than that from kidneys administered the vehicle (experiment 4; P < 0.001). A retrograde injection of bradykinin was without effect (experiment 5). 6. We conclude that renal kallikrein is involved in the regulation of urinary bicarbonate excretion. Increased intraluminal activity of the enzyme reduces, and decreased kallikrein activity increases, bicarbonate excretion. The enzyme may be a component of a negative feedback loop controlling the hydrogen ion activity of the extracellular space.
Marin-Grez
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Physiologisches Institut, Universität München, Germany.
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Odigie
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D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001639:Bicarbonates / Q000652:urine*; D001794:Blood Pressure / Q000502:physiology; D001920:Bradykinin / Q000493:pharmacokinetics / Q000494:pharmacology; D003243:Consciousness; D005260:Female; D007269:Injections, Intra-Arterial; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000502:physiology / Q000648:ultrastructure; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D012077:Renal Artery / Q000378:metabolism; D014513:Ureter / Q000378:metabolism
D001639:Bicarbonates; D007611:Aprotinin; D007610:Kallikreins; D001920:Bradykinin