Inhibition of Neurogulin-1/ErbB signaling in the RVLM leads to hypertension through reduced nitric oxide synthesis

Inhibition of Neuregulin-1/ErbB Signaling in the Rostral Ventrolateral Medulla Leads to Hypertension through Reduced Nitric Oxide Synthesis

Ryuichi Matsukawa, Yoshitaka Hirooka, Koji Ito, and Kenji Sunagawa
Background :Neuregulin-1 (NRG-1) binds to ErbB receptors. NRG-1/ ErbB signaling in the RVLM may have antihypertensive affects . It has been shown that ErbB signaling in RVLM is impaired in spontaneously hypertensive rats due to reduced ErbB2 expression.

Aim: The purpose of this study is to determine whether ErbB2 inhibition in the RVLM contributes to increasin blodd pressure via modulation of NO and GABA.

Methods:
They did intracisternal infusion of ErbB2 antagonist and the MAP and HR were monitored using telemetry. They also used siRNA in order to knock down ErbB2 expression in RVLM. Final they investigated protein expression of ErbB2, pErbB2 nNos, and eNOS in RVLM using western blot.

Results/ findings:
In response to the intracisternal infusion of the antagonist they found tha MAP, HR uNE were increased compared to the control. They also found that pErbB2, nNOS and eNOSwere lower in the treatment group compared to the control.In response to NOS blockade there was an increase in uNE on day 14 compared to before treatment. As for the ErbB2 siRNA, it lead to increased MAP and HR after 1 day of treatment . nNos and eNOS both were lower in ErbB2 siRNA group compared to control.

Conclusion:Study demostrates that attentuation of ErbB2 activity inRVLM causes hypertension by reducing NOS expression.