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Hypertension. 1985;7:905-912

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Hypertension, Vol 7, 905-912, Copyright © 1985 by American Heart Association


ARTICLES

Rat platelets activate high molecular weight atrial natriuretic peptides in vitro

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)