title: Neuregulin-1/ErbB signaling in rostral ventrolateral medulla is involved in blood pressure regulation as an antihypertensive system.
abstract: OBJECTIVE
  Neuregulin-1 (NRG-1), located in the central nervous system (CNS), plays an important role in synaptic function, neurite outgrowth, and survival of neurons and glia acting on the ErbB receptor family. However, the functional role of NRG-1/ErbB signaling in the CNS and blood pressure regulation is unknown, particularly in the rostral ventrolateral medulla (RVLM), a major vasomotor center. Thus, we investigated whether NRG-1/ErbB signaling in the RVLM is involved in blood pressure regulation.
  
  
  RESULTS
  Microinjection of NRG-1 into the RVLM decreased arterial blood pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) in Wistar rats. In contrast, microinjection of an ErbB2 or ErbB4 inhibitor into the RVLM increased arterial pressure, HR, and RSNA. ErbB2 expression levels in the brainstem were significantly lower in spontaneously hypertensive rats (SHRs) than in Wistar-Kyoto (WKY) rats. Depressor responses to NRG-1 and pressor responses to the ErbB2 inhibitor were significantly smaller in SHRs than in WKY rats (P < 0.05). Furthermore, the inhibition of ErbB2 expression in the RVLM by RNA interference significantly increased arterial pressure, HR, and urinary norepinephrine excretion in conscious WKY rats (P < 0.01).
  
  
  CONCLUSIONS
  Our findings indicate that the NRG-1/ErbB signaling in the RVLM has depressor and sympathoinhibitory effects. Reduced NRG/ErbB2 signaling in the RVLM may contribute to the neural mechanisms of hypertension.
authors: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors: Ryuichi
authors: R
authors: Matsukawa
authors: Yoshitaka
authors: Y
authors: Hirooka
authors: Masaaki
authors: M
authors: Nishihara
authors: Koji
authors: K
authors: Ito
authors: Kenji
authors: K
authors: Sunagawa
mesh_terms: D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure; D018815:Genes, erbB; D006339:Heart Rate; D006973:Hypertension / Q000503:physiopathology*; D008526:Medulla Oblongata / Q000378:metabolism* / Q000503:physiopathology; D020890:Neuregulin-1 / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011963:Receptors, GABA-A / Q000187:drug effects; D015398:Signal Transduction
chemical_list: D020890:Neuregulin-1; D034741:RNA, Small Interfering; D011963:Receptors, GABA-A