Modulation of Neuronal-Mediated Vasodepression and Bradycardia by Electroacupuncture through the Paraventricular Nucleus

Abstract

In rats that are not susceptible to EA (P5-6) modulation of the Bezold-Jarisch reflex, we look at the function of the CCK system in PVN during the parasympathoexcitatory cardiopulmonary reflex reactions. Bradycardia is a kind of arrhythmia, or irregular cardiac beat. When the heart beats less than 60 times per minute, it happens. An electrical impulse from the sinus node, a tiny region in the right atrium (right upper chamber) of the heart, starts a regular heartbeat. Between 60 and 100 times each minute, the heart contracts as a result of the energy flowing through it. It has been shown that parasympathoexcitatory reflex responses are modulated by electroacupuncture (EA) at P5-6 acupoints, which are connected to the median nerves, predominantly through central processing in the brainstem.  The precise function of the hypothalamus in this process is still unknown, despite the fact that it is widely accepted that EA affects the reductions in blood pressure and heart rate caused by neurally driven Bezold-Jarisch, cardiopulmonary reflex responses in the nucleus tractus solitarius and nucleus ambiguous. Sympathetic afferents are known to stimulate the hypothalamic paraventricular nucleus (PVN), which is crucial in controlling sympathetic outflow and sympathoexcitatory cardiovascular responses.  Additionally, vagal afferents have the ability to activate the PVN. However, little is known regarding the role of the PVN in controlling cardiopulmonary inhibitory hemodynamic responses. We proposed that EA suppresses the Bezold-Jarisch reflex responses by acting on the opioid system of the PVN, which is involved in the Bezold-Jarisch reflex responses. 

Rats were anesthetized, ventilated, and heart rate and blood pressure were monitored continuously throughout the experiment. Application of phenylbiguanide every 10 min close to the right atrium induced consistent depressor and bradycardia reflex responses with and without EA. To assess the cellular responses and evaluate the importance of PVN in the cardiopulmonary reflex responses, microinjections of kainic acid and kynurenic acid were performed. To investigate the mechanism of EA, PVN microinjections of naloxone were conducted. Additionally, extracellular recordings of PVN cardiovascular neurons were performed, focusing on vagal nerve-evoked activities to test the responses to EA. Iontophoresis was performed to study cellular responses to EA.

Unilateral microinjection of the depolarization blockade agent kainic acid or the glutamate receptor antagonist kynurenic acid into the PVN resulted in a noticeable reduction in these reflex responses.  Remarkably, in a significant majority, around 70% of the rats, a 30 min of bilateral EA at P5-6 acupoints reduced the depressor and bradycardia responses for at least 60 min. When naloxone was unilaterally microinjected into the PVN- it effectively reversed the inhibitory effects of EA on the cardiopulmonary reflex responses. Blockade of the CCK-1 receptors converted the non-responders into individuals who responded to EA. Furthermore, in these converted non-responders, PVN-microinjection with naloxone also reversed the EA-induced inhibition. It is worth noting that a 30-min EA at P5-6 led to a reduction in vagal-evoked activity of PVN cardiovascular neurons due to the activation of opioid receptors. These data indicate the pivotal role of the PVN in modulating inhibitory cardiopulmonary reflexes and its active participation in the EA-induced modulation of the neural-mediated vasodepressor and bradycardia responses. In conclusion, the opioid system reduces vagally triggered cardiovascular PVN neuronal activity, vasodepression, and bradycardia when 30 minutes of bilateral EA are applied to the P5-6 acupoints.