Excretion and metabolism of catecholamines by the isolated perfused rat kidney

Isolated perfused rat kidneys rapidly excreted unchanged epinephrine and nonepinephrine into the urine. Their metabolites accumulate both in the recirculating medium and in the urine. The fractional excretion of ³H epinephrine and ³H norepinephrine is 4.3 ± 0.4 and 2.5 ± 0.1, respectively, and their clearance is directly related to the glomerular filtration rate. No maximum tubular transport was observed even at very high perfusion medium concentrations. Renal metabolite degradation of epinephrine was significantly higher than that of norepinephrine during an average of 25 min of perfusion (29 ± 4% vs 15 ± 2%). Increased conversion of ³H epinephrine to ³H metanephrine accounted for this difference, conversion of ³H norepinephrine to ³H normethanephrine being comparatively small (22 ± 3% vs 8.3 ± 1.6%). Conversion to ³H vanillylmandelic acid was identical in both cases. Catechol acids were almost unmeasurable and conjugation did not occur. The rat kidney actively secretes epinephrine and norepinephrine in direct proportion to its plasma concentration and glomerular filtration rate. The kidney extracts approximately 2%/min of ³H epinephrine from the medium, 41% excreted unchanged. By contrast only 1.4%/min of ³H norepinephrine is extracted 59% excreted unchanged. These studies imply that measurement of free catecholamine excretion accurately reflects plasma catecholamine levels. Interpretation of urinary catecholamine excretion in different pathophysiologic states should take into account simultaneous changes in renal function as well as the fact that the kidney excretes and metabolizes epinephrine and norepinephrine at different rates.