Neuregulin‐1/erbB signaling in rostral ventrolateral medulla of brainstem is involved in blood pressure regulation alteration of major neurotransmitters

Abstract

BackgroundNeuregulin‐1 (NRG‐1) is a multifunctional modulator that acts through epidermal growth factor family of tyrosine kinase receptors, including erbB2‐4. In the central nervous system, NRG‐1/erbB pathway has been shown to affect both glutamatergic and GABAergic function. However, it is totally unknown if this signaling pathway is involved in central blood pressure regulation. Therefore, we determined if NRG‐1/erbB signaling in the rostral ventrolateral medulla (RVLM) contributes to blood pressure regulation by altering the major neurotranmsiiters' function.Methods and ResultsIn anesthetized male Wistar rats, we microinjected NRG‐1β(0.025 pmol), erbB2‐receptor antagonist (AG825: 1.0 pmol) into the RVLM. NRG‐1 decreased mean arterial pressure (MAP) and heart rate (HR) ΔMAP −23.2 ± 1.8 mmHg, Δ HR −40.7 ± 5.5 bpm, n=5), while AG825 increased MAP and HR (Δ MAP 19.2 ± 2.9 mmHg, ΔHR 16.8 ± 1.2 bpm, n=4). Pre‐microinjection of NMDA receptor antagonist (AP‐5) into the RVLM attenuated the AG825 induced‐pressor response (6.5 ± 1.2 mmHg). Pre‐microinjection of GABAA receptor antagonist (bicuculine) into the RVLM attenuated the NRG‐1β induced‐depressor response (−4.3 ± 2.5 mmHg).ConclusionNRG‐1/erbB signaling in the RVLM contributes to AP and HR regulation via the modulation of both glutamatergic and GABAergic function. This pathway in the RVLM is involved in neural control of blood pressure.