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 bala nce. 2. The bicarbonate concentration and the kallikrein activity in t he spontaneously voided urine of conscious rats (experiment 1) were in versely correlated (correlation coefficient (r)= -0.63, P < 0.0001). T he correlation was even greater when the urinary bicarbonate concentra tion 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 kall ikrein activity (P < 0.05) and increased bicarbonate excretion rate (P < 0.012). 4. Renal arterial infusion of aprotinin in barbiturate-anae sthetized 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 metab olic acidosis (base excess: control, 2.9 +/- 0.7mM (mean +/- S.E.M.);e xperimental, -8.1 +/- 0.7 mM; P < 0.05). 5. The bicarbonate concentrat ion of urine fractions obtained after retrograde injection of kallikre in through the ureter into the collecting duct system of barbiturate- anaesthetized rats was lower than that from kidneys administered the v ehicle (experiment 4; P < 0.001). A retrograde injection of bradykinin was without effect (experiment 5). 6. We conclude that renal kallikre in is involved in the regulation of urinary bicarbonate excretion. Inc reased intraluminal activity of the enzyme reduces, and decreased kall ikrein activity increases, bicarbonate excretion. The enzyme may be a component of a negative feedback loop controlling the hydrogen ion act ivity of the extracellular space.