AJP - Regulatory, Integrative and Comparative Physiology, Vol 254, Issue 5 809-R814, Copyright © 1988 by American Physiological Society
In vitro secretion of atrial natriuretic factor: receptor-mediated release of prohormone
A. T. Veress, S. Milojevic, C. Yip, T. G. Flynn and H. Sonnenberg
Department of Physiology, University of Toronto, Ontario, Canada.
Secretion of atrial natriuretic factor (ANF) in vivo is thought to be
mediated by atrial distension. We have shown previously that nonstretched
atria can release natriuretic activity in vitro when stimulated by certain
agonists. In the present study atrial appendages from freshly excised rat
hearts were incubated at 37 degrees C for up to 1 h in the presence of
either vasopressin (5 X 10(-9) mol/l) or angiotensin II (2.5 X 10(-7)
mol/l). Aliquots of postincubation media were injected intravenously into
anesthetized bioassay rats to determine natriuretic activity. Control
media, in which atria had been incubated without agonist, did not cause
natriuresis. Significant increases in sodium excretion were seen after
injection of media in which atria had been incubated in the presence of
either agonist. Injection of medium with the same agonist concentration did
not result in comparable natriuresis. Radioimmunoassay (RIA) indicated a
high concentration of immunoactive ANF in the natriuretic media. However,
radioreceptor assay (RRA) of the same media gave apparent ANF
concentrations that were lower by about three orders of magnitude. Because
the antibody used in the RIA cross reacts with ANF prohormone, whereas the
RRA is sensitive only to the active form, we concluded that
agonist-induced, stretch-independent release of ANF is in the form of
prohormone, which can be converted to the active hormone in the circulation
of the bioassay animal. The conclusion of prohormone release was confirmed
by liquid chromatography. The data thus suggest that receptor-mediated as
well as stretch-induced ANF secretion may be important in regulating the
activity of the ANF system.
