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Inhibitory effects of aprotinin on kallikrein and kininases in dog's blood
Author(s) -
POJDA S. M.,
VANE J. R.
Publication year - 1971
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1971.tb07140.x
Subject(s) - aprotinin , kallikrein , kinin , bradykinin , chemistry , pharmacology , jejunum , endocrinology , medicine , in vivo , blood pressure , anesthesia , biochemistry , enzyme , biology , receptor , microbiology and biotechnology
Summary1 The blood‐bathed organ technique was used in dogs to estimate kinin generation in the blood. Strips of cat jejunum were used as assay tissues. 2 Infusions of kallikrein at 0·5–8 mu/ml into the blood in the extracorporeal circuit led to a generation of kinin at 0·6–10 ng/ml. The kinin generated was at the same concentration after incubation of kallikrein with blood for 15 s or 120 seconds. Intravenous infusions of kallikrein at (8–125 mu/kg)/min led to similar blood concentrations of kinin. These infusions induced substantial falls in blood pressure. 3 Aprotinin inhibited the generation of kinin by kallikrein, but the concentration needed in vivo was 20,000 times higher than would be expected from the definition of the units. 4 After intravenous injection of large doses of aprotinin, the kallikrein‐inhibiting activity passed off within 40–60 minutes. At the same time, there was a gradual reduction in kininase activity, so that the half life of bradykinin in blood increased from a mean of 13 s to 40 seconds. This effect reached a maximum 1–3 h after injection of aprotinin. 5 It is suggested that a metabolite of aprotinin is responsible for the kininase inhibition and that this effect may limit the usefulness of aprotinin in man.