Hypertension, Vol 7, 905-912, Copyright © 1985 by American Heart Association
NC Trippodo, A Januszewicz, BL Pegram, FE Cole, N Kohashi, MB Kardon, AA MacPhee and ED Frohlich
Evidence suggests that the more biologically active low molecular weight
forms (less than 10,000) of rat atrial natriuretic peptides are
proteolytically derived from a less active precursor of higher molecular
weight. Conversion and activation could occur within the myocyte as well as
during circulation. The present study found that in vitro rat blood and
platelets were capable of converting the high molecular weight atrial
natriuretic peptides (greater than 10,000) to low molecular weight atrial
natriuretic peptides within minutes and that enhanced biological activity
attended the conversion. Rat high molecular weight peptides were partially
purified by gel filtration, lyophilized, and reconstituted in Krebs-Ringer
bicarbonate buffer. One milliliter of fresh rat blood was incubated with
the high molecular weight peptides at 37 degrees C for 2 minutes. After
centrifugation, the supernatant was fractionated on Sephadex G-75.
Natriuretic activity was determined by bioassay in anesthetized rats. In
contrast to the results following incubation of high molecular weight
peptides in Krebs- Ringer bicarbonate buffer alone, which showed that 95%
of the natriuretic activity remained in the high molecular weight peptide
region, the natriuretic activity of the blood-treated high molecular weight
peptides eluted almost exclusively in the low molecular weight peptide
region, which indicates conversion. Blood was separated into plasma,
erythrocytes, lymphocytes, and platelets. Conversion of high to low
molecular weight peptides occurred only after incubation with platelets.
Compared with control high molecular weight peptides, rat platelet-treated
high molecular weight peptides had significantly greater activity in
relaxing histamine-contracted rabbit aortic smooth muscle (p less than
0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Rat platelets activate high molecular weight atrial natriuretic peptides in vitro
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