Indomethacin abolishes core temperature, but not cardiovascular or renal, responses to lipopolysaccharide in conscious lambs

Abstract

1. Core temperature (Tc), cardiovascular and renal responses to lipopolysaccharide (LPS), as well as the role of endogenously produced prostaglandins (PG) in influencing these responses, were investigated in the present study in conscious, chronically instrumented lambs. 2. Core temperature, mean arterial pressure, heart rate (HR), renal blood flow (RBF) and several parameters of renal function were measured for 30 min before and for 5 h after intravenous injection of 0.03 μg/kg of the LPS Salmonella abortus equi (n = 9) or saline vehicle (n = 9). 3. After injection of LPS, Tc increased with a latency of 40 min, duration of 130 min and magnitude of 1.5°C. Mean arterial pressure increased within 110 min of LPS injection and then decreased below baseline within 5 h, concomitant with an increase in HR. There was a sustained increase in RBF after LPS injection and a significant increase in urinary flow rate, as well as Na(+) and Cl(-) excretion. 4. To determine the role of PGs in the responses to LPS observed, additional experiments were performed in another group of conscious lambs that had been pretreated with the non-selective cyclo-oxygenase inhibitor indomethacin (10 mg/kg; n = 6). 5. Although indomethacin abolished the Tc response to LPS, it had no significant effect on the cardiovascular and renal responses to LPS. There were no effects of saline vehicle on any of the variables measured. 6. These data provide evidence that, in conscious young lambs, cardiovascular and renal responses to LPS do not appear to be mediated by endogenously produced PGs and that they are independent of pyrogen-induced changes in Tc.