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Increased lipopolysaccharide‐induced hypothermia in neurogenic hypertension is caused by reduced hypothalamic PGE 2 production and increased heat loss
Author(s) -
Amorim Mateus R.,
Moreira Diego A.,
Santos Bruna M.,
Ferrari Gustavo D.,
Nogueira Jonatas E.,
de Deus Júnia L.,
Alberici Luciane C.,
Branco Luiz G. S.
Publication year - 2020
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp280321
Subject(s) - hypothermia , lipopolysaccharide , medicine , inflammation , thermoregulation , systemic inflammation , prostaglandin e2 , prostaglandin , blood pressure , oxidative stress , hypothalamus , endocrinology , core temperature
Key points 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 E 2 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) E 2 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 PGE 2 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 PGE 2 production, which are all associated with increased hypothermia mediated by increased heat loss, but not by heat production, in SHR.