1. Isolated human platelets were used to investigate the effect of atr
ial natriuretic peptide (ANP) on in vitro platelet aggregation induced
by epinephrine, ADP, collagen and 5-hydroxytryptamine. As a direct st
imulant of particulate guanylate cyclase, ANP is known to have no dire
ct effect on platelets which contain soluble guanylate cyclase. 2. In
our experiments ANP inhibited epinephrine- and partially ADP-induced a
ggregation in vitro and this effect was suggested to be the result of
an interaction of the peptide with adenylate cyclase in platelets. How
ever, the concentrations required to produce this effect were higher t
han those expected to be found in the circulation both physiologically
and pathologically. 3. We therefore conclude that though the peptide
may inhibit aggregation via adenylate cyclase activation, it is unlike
ly that ANP may play a direct role in preventing platelets aggregating
.