Vagus nerve stimulation ameliorates L-NAME-induced preeclampsia-like symptoms in rats through inhibition of the inflammatory response

Abstract

Background Preeclampsia is characterized by an excessive inflammatory response. Recent studies have shown that vagus nerve stimulation (VNS) has anti-inflammatory properties in vivo. This study aims to investigate whether VNS is safe for use during pregnancy and to explore the therapeutic potential and underlying mechanisms of VNS in PE. Methods Pregnant Sprague-Dawley rats were randomly chosen to receive N-nitro-L-arginine methyl ester (L-NAME)-containing water (preeclampsia-like mouse model) or saline (normal pregnancy control) daily at gestational days 14.5-20.5. VNS and the α7nAChR antagonist methyllycaconitine citrate (MLA, 1 mg/kg/d) were given daily at the same time. Results VNS decreased the high systolic blood pressure and urinary protein observed in the PE rats. In addition, VNS mitigated abnormal pregnancy outcomes. Moreover, VNS alleviated the inflammatory response by decreasing the levels of inflammatory cytokines. VNS significantly increased the expression of α7nAChR and attenuated the activation of NF-κB p65 in the placenta. Discussion Our findings indicate that maternal VNS treatment is safe during pregnancy and has a protective effect in a pregnant rat model of preeclampsia induced by L-NAME.

The involvement of long noncoding RNA APOA1-AS in the pathogenesis of preeclampsia

“…In this study, L-NAME was used to create a PE rat model, and elevated blood pressure and poor pregnancy were observed in rats, consistent with the results of several previous studies. 47–49 However, it was also found that APOA1-AS siRNA significantly ameliorated the L-NAME-induced increases in SBP and DBP in PE rats, suggesting that APOA1-AS downregulation could play a role in lowering blood pressure. In addition, APOA1-AS siRNA also reduced the expression levels of E-cadherin, ICAM-1 and VCAM-1 in placental tissues of PE rats, which further verified the in vitro experimental results.…”

TaVNS reduces inflammatory responses in a L-NAME-induced rat model of pre-eclampsia

“…In fact, through the activation of α7nAChR and the cholinergic anti-inflammatory pathway (CAP), the VNS inflammatory reflex is considered as a main neural control mechanism to prevent the production of proinflammatory mediators from innate immune cells (Borovikova et al, 2000). In a previous study, we reported that treatment with VNS significantly improved adverse pregnancy outcomes through anti-inflammatory pathway in L-NAME -induced PE model rats (Zheng et al, 2021). However, the clinical application of VNS is limited by its invasiveness.…”