Tachyphylaxis of the B1 kinin receptor in porcine endotoxin shock

Previous experiments in anesthetized pigs have demonstrated that blockade of the bradykinin B2 receptor in experimental endotoxin shock attenuates LPS-induced organ failure, lung dysfunction and mortality. Additional B1 receptor blockade in this situation seems to counteract the beneficial effects of B2 blockade. This suggests that the upregulation of B1 receptors during porcine LPS shock may be a useful mechanism of host defense. Furthermore, infusion of a B1 agonist during septic shock may be of therapeutic benefit. In order to prepare an experiment with B1 stimulation in LPS shock, we conducted a study in anesthetized pigs, in which the B1 receptor has been upregulated by infusion of bacterial lipopolysaccharide (LPS), by evaluating the effect of constant intravenous infusions of the B1 agonist des-Arg10-kallidin on the hypotensive response to bolus doses of this agonist. Following infusions of lipopolysaccharide from S. abortus equi, anesthetised pigs received repeated intra-arterial bolus injections of des-Arg10-kallidin before and during continuous infusions of this agonist in doses of 3, 10, 30 and 100 ng/kg/min. We found that all doses greater than 3 ng/kg/min produced attenuation of the hypotensive response produced by bolus administration of the B1 agonist des-Arg10-kallidin. We conclude that tachyphylaxis is an important feature to be considered in experiments with continuous administration of a B1 agonist in LPS shock.