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Tissue plasminogen activator release in vivo in response to vasoactive
agents
D Smith, M Gilbert and WG Owen
Release of tissue plasminogen activator into the circulation of rats in
response to intravascular injections of vasoactive agents is studied by
using a sensitive and specific clot lysis assay. Intra-arterial bradykinin
elicits a rapid and transient rise in circulating plasminogen activator,
which is maximum within one minute and is cleared within four to eight
minutes. The plasminogen activator is fibrin dependent and is neutralized
by an antiserum to human tissue- type plasminogen activator. Bradykinin is
1,000-fold more potent than the other agonists tested, which include
histamine, norepinephrine, epinephrine, eledoisin-related peptide,
arginine-vasopressin, lysine- vasopressin, desmopressin acetate, carbachol,
and acetylcholine. Potency of bradykinin is related to its amino acid
sequence. Sequential infusions of bradykinin produce a tachyphylactoid
response that could be overcome by increasing the dose of the sequential
bradykinin challenge. It is concluded that the characteristics of the
responses to bradykinin and other agents in vivo differ significantly from
those observed in isolated tissue preparations.
Volume 66,
Issue 4,
pp. 835-839,
10/01/1985
Copyright © 1985 by The American Society of Hematology
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