Electroacupuncture ameliorates chronic heart failure: the role of CRH neurons in the paraventricularnucleus of the hypothalamus

TL;DR

Electroacupuncture improves chronic heart failure by reducing overactivity in specific brain neurons linked to stress and heart function.

Contribution

This study reveals that electroacupuncture alleviates chronic heart failure by modulating CRH neurons in the hypothalamus.

Findings

EA reduced sympathetic overactivation and improved heart function in a rat model of chronic heart failure.

PVNCRH neuron inhibition mimicked the protective effects of EA, while their activation counteracted these effects.

EA's therapeutic effects were diminished when the PVN was lesioned, confirming its role in EA's mechanism.

Abstract

Chronic heart failure (CHF) constitutes the terminal stage of ischemic heart disease and is characterized by a high mortality rate. Our previous studies have demonstrated that electroacupuncture (EA) modulates the paraventricular nucleus (PVN) of the hypothalamus, thereby exerting a cardioprotective effect against myocardial ischemia. However, the specific mechanisms underlying the role of corticotropin-releasing hormone (CRH) neurons, which are critical for regulating sympathetic outflow and stress responses within the PVN, remain unclear in the context of CHF. Additionally, CHF has been proven to cause an imbalance in the autonomic nervous system. This study seeks to investigate whether EA can re-establish cardiac autonomic homeostasis and ameliorate CHF by modulating PVNCRH neurons, thereby suppressing excessive sympathetic outflow.

The CHF rat model was established via permanent ligation of the left anterior descending coronary artery. Subsequently, EA was administered at the HT7 (Shenmen) acupoint. ECG signals were recorded, and heart rate variability analyzed. The neural connection was demonstrated using viral tracing techniques. Electrophysiological techniques recorded PVN neuron activity, while echocardiography measured left ventricular function. ELISA detected serum N-terminal pro-brain natriuretic peptide and norepinephrine levels. Histological heart examination used staining methods, and c-Fos-positive neurons expression in the PVN was assessed. The PVN was lesioned with kainic acid, and PVNCRH neurons activity was modulated using chemogenetics.

This study indicated that EA significantly ameliorated CHF. In the CHF rat model, we observed excessive activation of the sympathetic nervous system, concomitant with an increased number of c-Fos-positive neurons in the PVN. EA intervention effectively reversed these changes. Viral tracing revealed neural connections between the heart, HT7 acupoint, and PVN. Following lesioning of the PVN, the therapeutic efficacy of EA was attenuated. Furthermore, chemogenetic experiments revealed that inhibiting the activity of PVNCRH neurons produced a protective effect against CHF similar to that of EA, whereas activating these neurons counteracted the protective effects of EA.

EA ameliorated CHF by inhibiting the activity of PVNCRH, suppressing sympathetic overactivation. These findings provided scientific evidence for the potential clinical application of acupuncture in cardiovascular disease management.

Figures