AJP - Heart and Circulatory Physiology, Vol 258, Issue 1 134-H139, Copyright © 1990 by American Physiological Society
ANF disappearance and tissue distribution in rats
J. Widimsky Jr, W. Debinski, O. Kuchel and N. T. Buu
Laboratory of the Autonomic Nervous System, Clinical Research Institute of Montreal, Hotel-Dieu Hospital, Quebec, Canada.
The disappearance of [125I]atrial natriuretic factor (ANF; Ser99-Tyr126)
from the circulation and its tissue distribution with or without nonlabeled
ANF pretreatment were investigated in normotensive Sprague-Dawley rats.
Preadministration of the cold peptide increased plasma radioactivity levels
for over 8 min following labeled ANF injection but did not change the
half-life of circulating labeled ANF. The metabolic clearance rate (MCR)
and volume of distribution in the first, second, and steady state phase
were significantly decreased after cold ANF pretreatment. Circulating
iodo-labeled ANF was taken up by several organs, even by tissues such as
fat or bone, but its urinary excretion was very low. The highest uptake was
found in the liver (16 +/- 1% of the injected dose), lung (14 +/- 1%), and
kidney (12 +/- 1%), diminishing by 21, 89, and 59%, respectively, after
cold ANF preinjection. The brain radioactivity was negligible implying an
inability of [125I]ANF to cross the blood-brain barrier. Our data
underscore the importance of the uptake-mediated, cold ANF
preadministration suppressible clearance of ANF from the circulation,
probably one of its basic elimination mechanisms. The liver, lung, and
kidney are probably the most important participants in the MCR of ANF.
