Increased Lipopolysaccharide‐Induced Hypothermia in Neurogenic Hypertension is caused by Reduced Hypothalamic PGE2 Production and Increased Heat Loss

Abstract

Brain‐mediated thermoregulatory changes in systemic inflammation (SI) induced by lipopolysaccharide (LPS) at a septic‐like model are characterized by hypothermia followed by fever which are associated with inadequate tissue oxygenation, multiple organs dysfunctions, and death. Hypertension is a prevalent chronic disease characterized by autonomic‐induced elevated and sustained blood pressure levels and spontaneously hypertensive rats (SHR) also have abnormal body core temperature (Tb) regulation and metabolic adjustments, by unknown mechanisms. The rationale of the present study was to find out the mechanisms involved in the thermoregulatory changes observed during SI in SHR. We combined Tb and skin temperature (Tsk) analysis, assess prostaglandin (PG) E2 levels in the anteroventral region of the hypothalamus (AVPO), indirect calorimetry, cardiovascular recordings, assays of inflammatory markers and evaluation of oxidative stress status in male Wistar and SHR that receive intravenous administration of LPS (1.5 mg.kg−1) or saline (CEUA #2017.1.585.58.9). As expected, LPS induced hypothermia followed by fever in Wistar whereas in SHR increased hypothermia and no fever were observed. These changes were associated with an increased Tsk in SHR in relation to Wistar (P < 0.05). Oxygen consumption and carbon dioxide production were significantly and similarly reduced in both SHR and Wistar rats during SI (P < 0.05). Interestingly, we measured increased AVPO PGE2 levels in Wistar during SI (P < 0.05), but not in SHR. LPS‐induced drop in MAP was significantly higher in SHR than in Wistar rats. Besides, LPS‐induced plasma and brain cytokines surges were blunted whereas oxidative stress was higher in SHR (P < 0.05). The present data are consistent with the notion that in SHR LPS‐induced SI leads to thermoregulatory changes mediated by the thermo effector mechanisms in the skin but not in energy expenditure and these events are associated with reduced hypothalamic PGE2.Support or Funding InformationFAPESP, CAPES and CNPq