The Reflex Sympathetic Activation Attenuates Systemic Inflammation in Unanesthetized Rats

다국어 초록 (Multilingual Abstract)

The literature reports that electrical activation or surgical denervation of the sympathetic nerves elicits anti‐inflammatory effects. Our previous study (American Heart Association’s Council on Hypertension 2016 Scientific Sessions: AP305) also indicated that sympathetic activation, by bilateral carotid occlusion (BCO) in unanesthetized rats, attenuates the release of pro‐inflammatory cytokines in an experimental model of sepsis. However, to expand the knowledge about the anti‐inflammatory potential of this arm of the autonomic nervous system, the objective of the present study was to investigate the role of global reflex sympathetic activation by BCO in a systemic inflammation induced by a low dose of lipopolysaccharide (LPS). For this, femoral artery and vein catheters were inserted into anesthetized Wistar Hannover male rats, for arterial pressure recording and LPS administration, respectively. Moreover, the subjects were implanted with pneumatic cuffs around the common carotid arteries for performing the BCO. On the next day, under unanesthetized rats, the arterial pressure was recorded continuously during 7 hours, including the baseline period. After baseline parameters recording, the BCO was performed for 20 s; and immediately after, LPS (60 μg/kg, i.v.) or saline was administrated. Blood samples were collected under different moments (90, 180, 270 and 360 min), after LPS or saline injection, for analyzing plasma cytokines (TNF, IL‐6, IL‐1β, and IL‐10) levels over time. As expected, BCO was effective to increase the arterial pressure, confirming the reflex sympathetic activation. Over time, no difference was observed among all groups concerning the arterial pressure; however, the groups which received LPS showed an increase in heart rate at 180, 270 and 360 min, compared with the saline group. However, the BCO did not change this response. Concerning the plasma cytokine levels, 90 min after LPS, BCO attenuated TNF and IL‐1β levels, as compared to LPS treated rats [TNF: 1831 ± 290 (n = 8) vs. 1326 ± 180 pg/mL (n = 8); IL‐1β: 212 ± 74 (n = 8) vs. 104 ± 39 pg/mL, (n = 8)]. BCO also increased the IL‐10 levels at 90 min [410 ± 55 (n = 8) vs. 730 ± 66 pg/mL (n = 8)]. Nevertheless, BCO did not change IL‐6 levels [IL‐6: 8389 ± 1480 (n = 8) vs. 8546 ± 1560 pg/mL (n = 8)]. No differences in plasma cytokine levels were observed at 180, 270 or 360 min after LPS, comparing the LPS group with the LPS+BCO group. In conclusion, these results suggest that the reflex sympathetic activation, in unanesthetized rats, attenuates plasma pro‐inflammatory cytokines and increase the anti‐inflammatory cytokine release in a model of systemic inflammation. These data provide support to previous evidence concerning the anti‐inflammatory effects of the sympathetic arm of the autonomic nervous system.
FAPESP (2017/05163‐6; 2013/20549‐7) and CNPq (402076/2016‐8).