COMPARISON OF HYPOTENSIVE RESPONSE TO AGGREGATED IGG OR TO BACTERIAL LPS IN RATS

Objective and Design: Rats treated with aggregated IgG (Aggr.) become ''refractory'' to the hypotensive action of a second dose of Aggr. The objective of this study was to assess the responsiveness of animals p retreated with Aggr. to bacterial LPS and vice versa. Material or Subj ects: Female Wistar rats (250-300 g) were used. Each experiment was ca rried on at least 4 animals. Treatment: A human IgG preparation contai ning 30% aggregates (10-16 mg/100 g) or E. coli serotype 0111.B4 (0.00 5-1 mg/100 g) was administered i.v. Certain groups of animals were pre treated with 1 mg/100 g GdCl3 or with 10 mg/100 g pentoxyphylline (PTX ). Methods: Arterial blood pressure was monitored in the carotis using a polyethylene cannula and an electronic tension meter. Tumor necrosi s factor alpha (TNF-alpha) activity was estimated by the use of an L-9 29 cell cytotoxicity assay.Results: Pretreatment of rats with a sublet hal dose of LPS impaired the hypotensive reaction of the animals to Ag gr. Rats made ''refractory'' to Aggr. reacted to the injection of LPS with hypotension and a second phase milder than in the controls. Hypot ension could not be elicited by Aggr. in rats pretreated with GdCl3. T he same pretreatment had no effect on the first phase of hypotension i nduced by intravenous injection of LPS, whilst a mitigation of the sec ond phase was observed. Infusion of PTX immediately prior to Aggr. adm inistration prevented the drop of blood pressure. A sizeable level of TNF-alpha was detected only later than blood pressure had reached its minimum level following Aggr. administration. Conclusions: Hypotension induced by LPS may involve a macrophage population broader than that responsible for the vascular action of Aggr. The data presented do not support a primary role for TNF-alpha in Aggr. induced hypotension.