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

1 Although endotoxaemia induces kinin B-1 receptors in several animal model s, this condition is not documented in primates. This study examined the up -regulation of haemodynamic and proinflammatory responses to the BI agonist des-Arg(10)-kallidin (dKD) in a non-human primate model. 2 Green monkeys (Cercopithecus aethiops St Kitts) received lipopolysacchari de (LPS; 90 mug kg-l) or saline intravenously. After 4 h, anaesthetized mon keys were canulated via the carotid artery to monitor blood pressure change s 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 c aptopril at 4 h to 56 days post-LPS. 3 LPS increased rectal temperature but did not affect blood pressure after 4 h. dKD reduced blood pressure (E-max: 27 +/- 4 mmHg; EC50: 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 gr oups. The selective Bi antagonist [Leu(9)]dKD (75 ng kg(-1) min(-1), intrav enously) abolished responses to dKD but not BK. 4 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-i nduced oedema was present and stable in all monkeys. Go-administration of [ Leu(9)]dKD (150 nmol) significantly reduced oedema induced by dKD (50 nmol) . 5 These results suggest LPS up-regulation of B1 receptor effects in green m onkeys. This non-human primate model may be suitable for testing new, selec tive BI antagonists with therapeutic potential as anti-inflammatory agents.