title: Sources of human urinary epinephrine.
abstract: The kidney is a likely source for some urinary epinephrine (E) since adrenalectomized animals and humans continue to excrete urinary E and the human kidney contains E synthesizing enzymes. We studied subjects during an intravenous infusion of 3H-E to determine the fraction of urinary E derived from the kidney. Eight normal subjects (CON) and 5 older, heavier hypertensives (OHH) ate a light breakfast along with ascorbic acid supplementation and had intravenous and arterial lines placed. They received an infusion of 3H-E and had an oral water load. During the final hour of 3H-E infusion, urine and arterial blood samples were collected for 3H-E and E levels. After the 3H-E infusion was abruptly discontinued, arterial blood samples were collected to measure 3H-E kinetics. The total body clearance of 3H-E was about 2,500 ml/min from plasma and clearance of 3H-E to urine was about 170 ml/min. CON had plasma E levels of 43 +/- 4 pg/ml. Their predicted rate of clearance of E from plasma to urine of 7,471 +/- 865 pg/min was less than (P = 0.018) the actual urinary E excretion of 15,037 +/- 2,625 pg/min. Thus, 43 +/- 9% of urinary E in CON was apparently derived from renal sources and not filtered from blood. Among OHH 85 +/- 4% of urinary E was derived from the kidney, significantly (P < 0.01) different from CON. The OHH also produced much more urinary E than predicted from plasma 3H-E clearance into urine (P = 0.03). A major fraction of urinary E is not filtered from the blood stream but is apparently derived from kidney. A small fraction of urinary E may be derived from E stored in nerve endings along with norepinephrine, but this probably represents less than 2% of urinary E. Renal cleavage of E sulfate into E may be another potential source of urinary E. Some, and perhaps most, urinary E not filtered from the bloodstream is derived from renal N-methylation of norepinephrine as the human kidney has two enzymes capable of converting norepinephrine to E. In conclusion, a major portion of urinary E is derived from the kidney and not filtered from the bloodstream. This is an important factor in the interpretation of urine E levels. Renal E could alter renal blood flow, electrolyte reabsorption, and renin release prior to excretion into urine.
authors.affiliation: Department of Medicine, University of California San Diego, USA. mziegler@UCSD.edu
authors.forename: M G
authors.initials: MG
authors.lastname: Ziegler
authors.forename: M
authors.initials: M
authors.lastname: Aung
authors.forename: B
authors.initials: B
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D001835:Body Weight; D004837:Epinephrine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine*; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008875:Middle Aged; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D014316:Tritium; D004837:Epinephrine