Xuebijing attenuates hypotension through the upregulation of angiotensin II type 1 receptor-associated protein 1 in rats suffering from heat stroke.

ABSTRACT

In our previous study, we demonstrated that Xuebijing (XBJ), a traditional Chinese medicine, attenuates hypotension in rats suffering from heatstroke (HS). However, the underlying mechanisms have not yet been fully elucidated. Thus, the current study was carried out to investigate the mechanisms underlying the effects of XBJ on hypotension n rats suffering from HS. For this purpose, 72 anesthetized rats were randomized into 3 groups and intravenously injected twice daily for 3 days with XBJ (4 ml/kg body weight, XBJ group) or phosphate­buffered saline (PBS) (HS and sham-operated groups). Models of HS were established in the HS and XBJ groups by placing the rats in a simulated climate chamber with a temperature of 40˚C and a humidity of 60%. Rectal temperature, arterial pressure and heart rate were monitored and recorded. Angiotensin Ⅱ (Ang Ⅱ) levels were increased during HS (shown by ELISA), and XBJ had no apparent effect on Ang Ⅱ levels. The levels of Ang Ⅱ type 1 (AT1) receptor surface expression and AT1 receptor-associated protein 1 (Arap1) were decreased during HS; however, these effects were attenuated by pre-treatment with XBJ (shown by RT-qPCR and western blot analysis). For in vitro experiments, rat macrophages pre-treated with XBJ were stimulated with lipopolysaccharide (LPS). Pre-treatment with XBJ induced a marked inhibitory effect on the release of pro-inflammatory cytokines in the LPS-stimulated macrophages. Furthermore, XBJ inhibited the activation of nuclear factor κB (NF-κB) induced by LPS in the macrophages. Taken together, our data demonstrate that XBJ promotes Arap1 expression by inhibiting the activation of the NF-κB signaling pathway and the release of pro-inflammatory cytokines, which may be the molecular mechanisms through which XBJ alleviates blood pressure reduction in rats suffering from HS.