Role of bradykinin in ovine endotoxemia

We determined if the cardiopulmonary response to endotoxin (LPS) is mediated by bradykinin (BK). Sheep (n = 30) were prepared for chronic study with cardiopulmonary catheters, and chronic lung lymph fistulae. They were divided into the following study groups: A) BK infusion; B) LPS; C) LPS with angiotensin converting enzyme inhibitor (ACEI); D) ACEI alone; E) LPS with BK antagonist. Cardiac index and mean arterial pressure fell (6.9 +/- 0.4 to 5.3 +/- 0.3 L/min/m2 and 93 +/- 4 to 72 +/- 3 mmHg, respectively), and pulmonary lymph flow increased (10.5 +/- 3.0 to 17.8 +/- 4.3 ml/hr) during BK infusion. Addition of ACEI during BK infusion reduced the amount of BK necessary to induce a comparable response (125 to 2 micrograms/kg/hr). Administration of ACEI to LPS animals did not significantly alter their cardiopulmonary responses. BK antagonist did not change the response to LPS. Although the kallikrein-kinin pathway is believed to be activated during the septic response, our data do not lend support for the hypothesis that bradykinin is an important mediator of the cardiopulmonary changes.