Direct activation of tachykinin receptors within baroreflex afferent pathway and neurocontrol of blood pressure regulation

Aim: Substance P (SP) causes vasodilation and blood pressure (BP) reduction. However, the involvement of tachykinin receptors (NKRs) within baroreflex afferent pathway in SP- mediated BP regulation is largely unknown. Methods: Under control and hypertensive condition, NKRs’ expressions were evalu- ated in nodose (NG) and nucleus of tractus solitary (NTS) of male, female, and ova- riectomized (OVX) rats; BP was recorded after microinjection of SP and NKRs agonists into NG; Baroreceptor sensitivity (BRS) was tested as well. Results: Immunostaining and immunoblotting data showed that NK1R and NK2R were estrogen- dependently expressed on myelinated and unmyelinated afferents in NG. A functional study showed that BP was reduced dose- dependently by SP micro- injection, which was more dramatic in males and can be mimicked by NK1R and NK2R agonists. Notably, further BP elevation and BRS dysfunction were confirmed in desoxycorticosterone acetate (DOCA)- salt model in OVX compared with DOCA- salt model in intact female rats. Additionally, similar changes in NKRs’ expression in NG were also detected using DOCA- salt and SHR. Compared with NG, inversed ex- pression profiles of NKRs were also found in NTS with either gender. Conclusion: The estrogen- dependent NKRs’ expression in baroreflex afferent path- way participates at least partially in sexual- dimorphic and SP- mediated BP regulation under physiological and hypertensive conditions.