The action of Hoe 140 on the bradykinin-induced splenic pressor reflex of the anaesthetized cat.
1. Intrasplenic injection of bradykinin (BK) induced a dose-dependent pressor response in the anaesthetized cat, with an ED50 of 0.98 +/- 0.43 nmol. In contrast, intrasplenic administration of desArg9bradykinin (desArg9BK) was without significant effect at doses of up to 200 nmol. 2. Intravenously administered BK induced a dose-dependent depressor response in the anaesthetized cat, with an ED50 of 0.86 +/- 0.09 nmol kg-1. desArg9BK was again without significant effect in this system at doses of up to 200 nmol kg-1. 3. Both the pressor and depressor responses to BK were antagonized to a similar degree in a dose-dependent manner by Hoe 140 (10 and 100 nmol kg-1, i.v.). 4. At these doses, Hoe 140 appears to be a specific BK antagonist as it was ineffective against pressor responses to intrasplenic injection of capsaicin (5 nmol), while blocking those to an approximately equieffective dose of BK (1 nmol) in a dose-dependent fashion. 5. Both the pressor response to intrasplenic BK and the depressor response to intravenous BK in the anaesthetized cat appear to be mediated by B2-receptors. This model may be useful in the quantitative determination of the antinociceptive potency of BK antagonists.
Louttit
J B
JB
Department of Cardiovascular and Respiratory Pharmacology, Glaxo Group Research Ltd., Ware, Hertfordshire.
Coleman
R A
RA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D018002:Receptors, Bradykinin / Q000502:physiology; D012018:Reflex / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects* / Q000502:physiology
D065168:Bradykinin Receptor Antagonists; D018002:Receptors, Bradykinin; C065679:icatibant; D001920:Bradykinin