Induction of a B1-receptor mediating hypotensive response in young brown Norway rats

A hypotensive response to intravenously injected des-Arg9-bradykinin was elicited in young male Brown Norway rats (8-12 weeks-old), when the rats were intravenously injected with endotoxin (30 micrograms/kg) 24 h before they were repeatedly injected with bradykinin or des-Arg9-bradykinin. The potency of this inducible dose-dependent hypotensive response to des-Arg9-bradykinin was comparable to that induced by bradykinin on a molar base (3-30 nmol/kg). A hypotensive response to des-Arg9-bradykinin could also be induced when the rats were pretreated with endotoxin 6 h before. However, the potency of the response was less than that induced by 24-h pretreatment. This inducible response to des-Arg9-bradykinin did not occur in old rats (8-10 months old). Intravenous infusion of a B1-receptor antagonist, des-Arg9-[Leu8]-bradykinin, suppressed the hypotensive response of des-Arg9-bradykinin. These results suggest that the B1-receptor, mediating hypotension in rats, was inducible through time-dependent and age-dependent sensitization by endotoxin pretreatment.