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.

Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice

“…In this study, no effects of chronic indomethacin treatment were observed in either stressed or non-stressed animals. Little is known about the effects of indomethacin on anxiety, but Smith et al [99] reported that indomethacin had no significant effect on the cardiovascular response of conscious lambs to lipopolysaccharide. Therefore, it is not surprising that our study observed the inefficacy of indomethacin in reducing symptoms of anxiety in stressed mice.…”

Haemodynamic responses to angiotensin II in conscious lambs: role of nitric oxide and prostaglandins

“…More recently, we showed that there is an interaction between ANG II and NO in influencing cardiovascular homeostasis as well as the arterial baroreflex of heart rate early in life, which appears to be developmentally regulated [46]. We have also previously reported on the haemodynamic responses to INDO alone [12,13,39], as well as L-NAME alone [30][31][32]46] in conscious lambs at different stages of post-natal maturation. To these findings, the present observations support a further modulatory role for PGs in influencing the vasoconstrictor effects of ANG II soon after birth.…”