Abstract
This study aims to determine whether toll-like receptor 4 (TLR4)-mediated inflammation in rostral ventrolateral medulla (RVLM) causes sympathetic overactivity leading to preeclampsia (PE) and if TLR4 inhibition with hydrogen sulfide (H2S) would reduce PE severity. Thirty patients with PE and 30 pregnant controls were involved. PE in rats was induced through deoxycorticosterone acetate and normal saline. NaHS (donor of H2S), lipopolysaccharide (LPS) (TLR4 agonist), and TAK-242 (TLR4 inhibitor) were injected in lateral cerebral ventricle to investigate their effect on microglia-mediated inflammation in RVLM, sympathetic activation, and PE symptoms. In patients with PE, plasma levels of NE, TNF-α, and interleukin-1β were high compared with those of controls, whereas levels of H2S were low. Rats with PE showed an increased amount of renal sympathetic nerve activity and plasma levels of NE, with decreased H2S levels in RVLM. Microglia-mediated inflammation was observed in the RVLM of PE rats. Central infusion of LPS in pregnant rats induced microglia-mediated inflammation, sympathetic nervous tension, and PE-like symptoms, whereas TAK-242 reduced PE symptoms. NaHS treatment lessened microglia-mediated inflammation in the RVLM, sympathetic tension, and symptoms of PE both in PE rats and LPS-treating pregnant rats.These results suggest that inflammation in the RVLM caused by microglial activation might contribute to the progression of PE via an overactive sympathetic system. H2S could reduce PE via inhibiting inflammation in the RVLM. These results might provide a new target for the treatment of PE.