The mechanisms involved in
hypothermia and
fever during systemic
inflammation (SI) remain largely unknown. Our data support the contention that brain-mediated mechanisms are different in
hypertension during SI. Considering that, clinically, it is not easy to assess all mechanisms involved in cardiovascular and thermoregulatory control during SI, the present study sheds light on these integrated mechanisms that may be triggered simultaneously in septic hypertensive patients. The result obtained demonstrate that, in
lipopolysaccharide-induced SI, an increased
hypothermia is observed in neurogenic
hypertension, which is caused by reduced hypothalamic
prostaglandin E2 production and increased heat loss in conscious rats. Therefore, the results of the present study provide useful insight for clinical trials evaluating the thermoregulatory outcomes of septic patients with
hypertension.
ABSTRACT:
Hypertension is a prevalent disease characterized by autonomic-induced elevated and sustained blood pressure levels and abnormal body core temperature (Tb) regulation. The present study aimed to determine the brain-mediated mechanisms involved in the thermoregulatory changes observed during
lipopolysaccharide (LPS)-induced systemic
inflammation (SI; at a septic-like model) in spontaneously hypertensive rats (SHR). We combined Tb and skin temperature (Tsk) analysis, assessment of
prostaglandin (PG) E2 levels (the proximal mediator of
fever) in the anteroventral region of the hypothalamus (AVPO; an important site for Tb control), oxygen consumption analysis, cardiovascular recordings, assays of inflammatory markers, and evaluation of oxidative stress in the plasma and brain of male Wistar rats and SHR that had received LPS (1.5 mg kg-1 ) or saline. LPS
induced hypothermia followed by
fever in Wistar rats, whereas, in SHR, a maintained
hypothermia without
fever were observed. These thermoregulatory responses were associated with an increased heat loss in SHR compared to Wistar rats. We measured LPS-induced increased
PGE2 levels in the AVPO in Wistar rats, but not in SHR. The LPS-induced drop in blood pressure was higher in SHR than in Wistar rats. Furthermore, LPS-induced plasma and brain [regions involved in autonomic control: nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM)]
cytokine surges were blunted, whereas oxidative stress was higher in SHR. LPS-induced SI leads to blunted
cytokine surges both systemically (plasma) and centrally (NTS and RVLM) and reduced hypothalamic
PGE2 production, which are all associated with increased
hypothermia mediated by increased heat loss, but not by heat production, in SHR.