Role of perfusate hydrogen ion activity in kallikrein release from isolated rat kidneys

The present experiments were performed to investigate whether renal kallikrein release by isolated perfused rat kidneys correlates with acid-base-related parameters. Kallikrein excretion per millilitre of glomerular filtrate was inversely correlated with perfusate pH (r = -0.49, P < 0.001) and HCO3- concentration (r = -0.46, P < 0.005). A direct relationship between kallikrein excretion per millilitre of glomerular filtrate and urinary Na+/K+ ratio was found (r = 0.59, P < 0.001). Some 86% of the variability (F ratio 110, P < 0.00001) of urinary kallikrein activity was attributable to the perfusate pH and the urinary cation ratio. Therefore, urinary kallikrein activity was highly correlated with perfusate H+ activity corrected by the urinary Na+/K+ ratio (r = 0.92, P < 0.0001). Kallikrein secretion into the distal tubular fluid appears to be regulated by blood H+ activity, and modulated by factors that affect the distal Na+ and K+ handling. The HCO3 - excretion rate was inversely correlated with the urinary kallikrein activity (r = -0.62, P < 0.001). This finding confirms previous data from the author's laboratory showing a kallikrein involvement in the regulation of HCO3- secretion in rats and rabbits. Kallikrein probably transduces the sensing of interstitial fluid H+ activity by the connecting tubule cells into an appropriate translocation of HCO3- or H+ to the tubular lumen by the intercalated cells.