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

Abstract

Beyond the regulation of cardiovascular function, baroreceptor afferents play polymodal roles in health and disease. Sepsis is a life-threatening condition characterized by systemic inflammation (SI) and hemodynamic dysfunction. We hypothesized that baroreceptor denervation worsens lipopolysaccharide (LPS) induced-hemodynamic collapse and SI in conscious rats. We combined: (a) hemodynamic and thermoregulatory recordings after LPS administration at a septic-like non-lethal dose (b) analysis of the cardiovascular complexity, (c) evaluation of vascular function in mesenteric resistance vessels, and (d) measurements of inflammatory cytokines (plasma and spleen). LPS-induced drop in blood pressure was higher in sino-aortic denervated (SAD) rats. LPS-induced hemodynamic collapse was associated with SAD-dependent autonomic disbalance. LPS-induced vascular dysfunction was not affected by SAD. Surprisingly, SAD blunted LPS-induced surges of plasma and spleen cytokines. These data indicate that baroreceptor afferents are key to alleviate LPS-induced hemodynamic collapse, affecting the autonomic control of cardiovascular function, without affecting resistance blood vessels. Moreover, baroreflex modulation of the LPS-induced SI and hemodynamic collapse are not dependent of each other given that baroreceptor denervation worsened hypotension and reduced SI.

Increased lipopolysaccharide‐induced hypothermia in neurogenic hypertension is caused by reduced hypothalamic PGE2 production and increased heat loss

“…We also investigated the effects of SI on haemodynamic parameters in SHR and Wistar rats. In Wistar rats, LPS administration induces characteristic biphasic drop in MAP associated with tachycardia (Saia et al 2013;Amorim et al 2019Amorim et al , 2020. On the other hand, the LPS-induced drop in MAP was significantly higher in SHR than in Wistar rats, whereas LPS-induced tachycardia was blunted in these animals ( Fig.…”

“…Considering the existing evidence regarding the reduction in the baroreflex gain in SHR rats (Head & Adams, 1988), as well as our own data, we suggest that the reduction baroreflex gain in SHR rats is one of the mechanisms involved in the enhancement of the LPS-induced drop in blood pressure in SHR. Regarding HR, a blunted tachycardia with greater drop in blood pressure in SHR may be related, at least in part, to the baroreflex (Amorim et al 2019(Amorim et al , 2020. Recent studies have suggested that endovascular baroreflex amplification therapy, which increases the stretch of the carotid and sinus activating the baroreceptors, may be a good alternative in the management of hypertensive patients who are resistant to anti-hypertensive medication (van Kleef et al 2018).…”

“…2013; Amorim et al . 2019, 2020). On the other hand, the LPS‐induced drop in MAP was significantly higher in SHR than in Wistar rats, whereas LPS‐induced tachycardia was blunted in these animals (Fig.…”

“…Regarding HR, a blunted tachycardia with greater drop in blood pressure in SHR may be related, at least in part, to the baroreflex (Amorim et al . 2019, 2020). Recent studies have suggested that endovascular baroreflex amplification therapy, which increases the stretch of the carotid and sinus activating the baroreceptors, may be a good alternative in the management of hypertensive patients who are resistant to anti‐hypertensive medication (van Kleef et al .…”

“…These results are in accordance with our previous studies reporting that animals submitted to sino‐aortic denervation (a useful experimental model for baroreceptor afferents removal, which, may also damage CBs) present a significantly enhancement in LPS‐induced drop in blood pressure (Amorim et al . 2020). Interestingly, bilateral CB ablation affected the LPS‐induced haemodynamic changes in SHR (Fig.…”