(613.1) Baroreflex Activation Contributes to the Progression of the Systemic Inflammatory Response in Unanesthetized Rats

Poster Board Number: E565

Luiz Cesarino (Ribeirão Preto Medical School), Fernanda Brognara (Ribeirão Preto College of Nursing), Jaci Castania (Ribeirão Preto Medical School), Helio Salgado (Ribeirão Preto Medical School)

Our laboratory showed that electrical activation of the baroreflex could modulate the immune system by controlling the inflammatory response in rats. However, no study has investigated whether physiological reflex activation of the baroreflex also has an anti-inflammatory effect. Therefore, the objective of the present study was to investigate the effect of physiological activation of the baroreflex in unanesthetized rats, through abdominal aortic coarctation (AAC), on the systemic inflammatory response elicited by lipopolysaccharide (LPS) administration. Sprague-Dawley male rats (250-300g) were anesthetized for placing, surgically, a cuff around the abdominal aorta and catheters into the carotid artery and femoral vein. On the next day, the hemodynamic parameters were recorded in the unanesthetized animals. Subsequently, the AAC was carried out for 2 min, followed by the administration of LPS (1.5 mg/kg, i.v.) or saline in the control subjects. After 90 min, blood and spleen samples were collected for subsequent cytokine analysis. As expected, compared to baseline, AAC increased systolic (122 ± 5 vs. 173 ± 10 mmHg), diastolic (90 ± 3 vs. 105 ± 4 mmHg), and mean arterial pressure (106 ± 4 vs. 131 ± 6 mmHg), and reduced heart rate (365 ± 25 vs. 306 ± 17 bpm), confirming the reflex activation of the baroreflex. However, the administration of LPS promoted an increase in heart rate (361 ± 11 vs. 428 ± 21 bpm) over time. Of note, the AAC group associated with LPS administration exhibited, 90 min after LPS administration, a fall in mean arterial pressure (98 ± 7 vs. 88 ± 7 mmHg), combined with an increase in heart rate (362 ± 15 vs. 470 ± 16 bpm). Moreover, compared to the group which received only LPS, the AAC associated with LPS increased the levels of cytokines (IL-6 and IL-10) in plasma (IL-6: 4505 ± 1294 vs. 8782 ± 520 pg/mL; IL-10: 5 ± 5 vs. 1079 ± 232 pg/mL) and spleen (IL-6: 3 ± 1 vs. 20 ± 3 pg/mg of tissue; IL-10: 0.1 ± 0.04 vs. 2 ± 0.4 pg/mg of tissue); potentiating, therefore, the release of cytokines after the induction of the inflammatory process. In conclusion, physiological baroreflex activation elicits a modulatory effect of the immune response during the systemic inflammation elicited by LPS, facilitating the inflammatory process and potentiating the hemodynamic responses promoted by the administration of LPS. Thus, this study showed for the first time that physiological baroreflex activation, through AAC, plays a role in the progression of the inflammatory process.

FAPESP (Fundaamp;ccedil;amp;atilde;o de Amparo amp;agrave; Pesquisa do Estado de Samp;atilde;o Paulo); Processes: #2020/06043-7, 2020/08312-5, and 2021/03764-8).