Neuropeptide Y stabilizes body temperature and prevents hypotension in endotoxaemic rats

The on-going high mortality from sepsis motivates continuous research for novel therapeutic strategies. Neuropeptide Y (NPY), a sympathetic neurotransmitter, has been shown to increase survival in experimental septic shock in rats. This protective effect might be due to immunological, cardiovascular or thermoregulatory effects. The aim of this study was to examine the in vivo effect of peripherally administered NPY on body temperature, blood pressure and heart rate in endotoxaemic animals. In order to obtain clinically relevant data, various physiological parameters were monitored in parallel via radio-telemetry in chronically intravenously cannulated, freely behaving rats. Rats received a sublethal bolus of lipopolysaccharide (LPS, 100 μg kg^-1 I.V.) and the three parameters were continuously recorded for 72 h. Endotoxaemic rats showed a long-lasting hypotension, an initial hypothermia (-0.5°C), followed by a prolonged febrile phase (+1.6°C 6 h after endotoxin challenge) associated with a decrease of the circadian rhythm amplitude of temperature. Pretreatment with NPY (160 pmol kg^-1 I.V. over 75 min) prevented hypotension and significantly stabilized body temperature immediately following the application. The febrile phase was effectively reduced for at least 72 h. These telemetrically obtained findings clearly demonstrate that pretreatment with NPY positively influences two life-threatening symptoms in endotoxaemia and might be a future option for a successful clinical treatment regimen.