Figure 2.

Chemical or surgical vagotomy blocks the protective action of intracerebral CNI-1493. (A) Effects of bilateral cervical vagotomy vs. sham surgery on the action of i.c.v. CNI-1493 (ng/kg) during endotoxemia, expressed as the percentage of starting MABP. CNI-1493 (1.0 ng/kg) was administered i.c.v., followed 60 min later by endotoxin (15 mg/kg, intravenously). Note that surgical vagotomy eliminated the protective effects of 1.0 ng CNI-1493/kg, i.c.v. against LPS-induced hypotension. (B) Effects of intravenous saline treatment (control) vs. atropine blockade on the action of i.c.v. administered CNI-1493 during endotoxemia, expressed as the percentage of starting MABP. CNI-1493 (1.0 ng/kg, i.c.v.) was administered to animals treated with atropine (1 mg/kg/h, intravenously) to block vagus nerve activity. Note that chemical vagotomy abolished the protective effect of i.c.v. CNI-1493 against LPS-induced hypotension. (C) Serum TNF levels after i.c.v. CNI-1493 injection 60 min after LPS infusion. On the left, all animals received an i.c.v. injection of vehicle. On the right, animals received CNI-1493 (1.0 ng/kg, i.c.v.). In both panels, “Ctrl” refers to animals that received atropine vehicle (saline), while “Sham” identifies those animals in which the vagus nerves were exposed, but not surgically divided. Note that chemical vagotomy and surgical vagotomy both significantly attenuated the protective effects of CNI-1493 (1.0 ng/kg, i.c.v.) against LPS-induced TNF release as compared with vehicle.