INFLUENCE OF INDOMETHACIN ON THE HEMODYNAMIC-EFFECTS OF LIPOPOLYSACCHARIDE IN RATS

This study was undertaken to evaluate the influence of the cyclooxygen ase inhibitor indomethacin on the time course of the haemodynamic effe cts of lipopolysaccharide (LPS) intravenous infusion (10 mg . kg(-1). h(-1)) in anaesthetized rats. LPS infusion produced a rapid (within 10 min) and prolonged (over the 90 min observation period) fall in mean arterial blood pressure (MABP) and a decrease in the pressor responses to noradrenaline (NA, 0.1, 0.3 and 1 mu g . kg(-1), intravenously [iv ]) elicited 60 and 90 min after the onset of LPS infusion. Indomethaci n (7 mg . kg(-1) iv 30 min prior to the onset of saline of LPS infusio n), which by itself did not affect basal MABP nor reactivity to NA in control rats significantly attenuated the fall in MABP observed within 20 min after the onset of LPS infusion (but did not significantly mod ify the hypotension observed between 30 and 90 min). Indomethacin also completely prevented the hyporeactivity to NA observed 60 min after t he onset of LPS infusion, but it did so only partially at 90 min. Aort ic rings removed from LPS or LPS + indomethacin-treated rats showed as identical profile of contractile reactivity (hyporesponsiveness to NA , relaxation to L-arginine, and restoration of the contractile respons e by methylene blue). These results suggest that in this model, cycloo xygenase products are involved in the early haemodynamic effects of LP S. However, they do not seem to play an obligatory role in the onset o f longer term haemodynamic changes.