Endotoxin sensitization to kinin B 1 receptor agonist in a non‐human primate model: haemodynamic and pro‐inflammatory effects

Although endotoxaemia induces kinin B 1 receptors in several animal models, this condition is not documented in primates. This study examined the up‐regulation of haemodynamic and pro‐inflammatory responses to the B 1 agonist des‐Arg 10 ‐kallidin (dKD) in a non‐human primate model. Green monkeys ( Cercopithecus aethiops St Kitts ) received lipopolysaccharide (LPS; 90 μg kg −1 ) or saline intravenously. After 4 h, anaesthetized monkeys were canulated via the carotid artery to monitor blood pressure changes following intra‐arterial injections of dKD or the B 2 agonist bradykinin (BK). Oedema induced by subcutaneous kinin administration was evaluated as the increase in ventral skin folds in anaesthetized monkeys injected with captopril at 4 h to 56 days post‐LPS. LPS increased rectal temperature but did not affect blood pressure after 4 h. dKD reduced blood pressure (E max : 27±4 mmHg; EC 50 : 130 pmol kg −1 ) and increased heart rate (E max : 33 b.p.m.) only after LPS. In contrast, the dose‐dependent fall in blood pressure with BK was comparable in all groups. The selective B 1 antagonist [Leu 9 ]dKD (75 ng kg −1  min −1 , intravenously) abolished responses to dKD but not BK. dKD injection induced oedema dose‐dependently (2.4±0.1 mm at 150 nmol) only following LPS (at 4 h to 12 days but not 56 days). In contrast, BK‐induced oedema was present and stable in all monkeys. Co‐administration of [Leu 9 ]dKD (150 nmol) significantly reduced oedema induced by dKD (50 nmol). These results suggest LPS up‐regulation of B 1 receptor effects in green monkeys. This non‐human primate model may be suitable for testing new, selective B 1 antagonists with therapeutic potential as anti‐inflammatory agents.British Journal of Pharmacology (2001) 132 , 327–335; doi: 10.1038/sj.bjp.0703748