Baroreflex stimulation attenuates central but not peripheral inflammation in conscious endotoxemic rats

Abstract

We previously reported that activation of the baroreflex, a critical physiological mechanism controlling cardiovascular homeostasis, through electrical stimulation of the aortic depressor nerve attenuates joint inflammation in experimental arthritis. However, it is unknown whether baroreflex activation can control systemic inflammation. Here, we investigate whether baroreflex activation controls systemic inflammation in conscious endotoxemic rats. Animals underwent sham or electrical aortic depressor nerve stimulation initiated 10 min prior to a lipopolysaccharide (LPS) challenge, while inflammatory cytokine levels were measured in the blood, spleen, heart and hypothalamus 90 min after LPS treatment. Baroreflex activation did not affect LPS-induced levels of pro-inflammatory (tumor necrosis factor, interleukin 1β and interleukin 6) or anti-inflammatory (interleukin 10) cytokines in the periphery (heart, spleen and blood). However, baroreflex stimulation attenuated LPS-induced levels of all these cytokines in the hypothalamus. Notably, these results indicate that the central anti-inflammatory mechanism induced by baroreflex stimulation is independent of cardiovascular alterations, since aortic depressor nerve stimulation that failed to induce hemodynamic changes was also efficient at inhibiting inflammatory cytokines in the hypothalamus. Thus, aortic depressor nerve stimulation might represent a novel therapeutic strategy for neuroprotection, modulating inflammation in the central nervous system.

Baroreceptor denervation reduces inflammatory status but worsens cardiovascular collapse during systemic inflammation

“…7). These findings indicate that baroreflex does modulate the LPS-induced peripheral cytokine surges and adds new information to a previous study that documented that electrical baroreflex stimulation inhibits LPS-induced pro-inflammatory cytokines surges not in the periphery but in the brain 20 . A putative mechanism by which sino-aortic afferents may play a modulatory effect in the LPS-induced IL-6 and IL-10 plasma surges may be related to macrophages polarization, a highly heterogeneous cell population, during SI.…”

“…More recently, it has been shown that baroreceptor afferents play a key role of mediating LPS-induced cardiovascular collapse [16][17][18][19] . Moreover, in SI, electrical baroreflex stimulation in rats has been reported to blunt LPS-induced production of cytokines in the hypothalamus 20 , indicating an anti-inflammatory role played by aortic depressor nerve stimulation. However, the involvement of the baroreceptors afferents in the systemic inflammatory status has not received the same attention, neither its putative link with the cardiovascular system during SI.…”

Baroreceptor denervation reduces inflammatory status and worsens cardiovascular collapse during systemic inflammation

“…6). These findings indicate that baroreflex does modulate the LPS-induced peripheral cytokine surges and adds new information to a previous study that documented that electrical baroreflex stimulation inhibits LPS-induced pro-inflammatory cytokines surges not in the periphery but in the brain (19). A putative mechanism by which sino-aortic afferents may play a modulatory effect in the LPS-induced IL-6 and IL-10 plasma surges may be related to macrophages polarization, a highly heterogeneous cell population, during SI.…”

“…Considering that baroreflex stimulation downregulates pro-inflammatory cytokines in hypothalamus, but not in plasma, heart and spleen (19) we hypothesized that SAD worsens cytokines surges in plasma. Contrary to our expectations, after SAD, LPS-induced surges of cytokines were blunted in plasma and spleen (Fig 8.)…”

“…More recently, it has been shown the role of baroreceptor afferents mediating LPS-induced cardiovascular collapse (15–18). Moreover, in SI, electrical baroreflex stimulation in rats has been reported to blunt LPS-induced production of cytokines in the hypothalamus (19), indicating an anti-inflammatory role played by aortic depressor nerve stimulation. However, the involvement of the baroreceptors afferents in the inflammatory status has not received the same attention, neither its putative relation with the cardiovascular system.…”