Responses Of Neurons In Paraventricular Nucleus To Activation Of Cardiac Afferents And Acute Myocardial Ischemia In Rats

BackgroundThe cardiac sympathetic afferent reflex (CSAR) is a sympatho-excitatory reflex to increase sympathetic outflow and arterial pressure. The CSAR can be induced by directly stimulating the cardiac sympathetic afferent nerves, or by stimulating the sympathetic afferent endings innervating the heart with epicardial application of capsaicin, bradykinin, adenosine or hydrogen peroxide. Our previous studies have shown that the enhanced CSAR is partially contributed to the increased sympathetic outflow in chronic heart failure and hypertension.The paraventricular nucleus (PVN) is an important integrative site in the control of cardiovascular activity and sympathetic outflow. We have found that the Ang II and AT1 receptors in PVN are involved in the enhanced CSAR in CHF rats. However, there is no electrophysiological evidence to indicate the activity of neurons in the PVN during the activation of cardiac afferents or myocardial ischemia as yet. The present study was designed to more conclusively demonstrate that the PVN is an important component of the central neurocircuitry of the CSAR and further elucidate the central mechanism responsible for modulation of the CSAR.Objective1. The effects of activation of cardiac sympathetic afferents with capsaicin, bradykinin, adenosine or hydrogen peroxide on the activity of neurons in the PVN with extracellular single-unit recording method.2. The response of the PVN neurons to the cardiac afferent stimulation was compared between the rats with vagotomy and baroreceptor denervation and the intact rats.3. The effects of acute myocardial ischemia on the activity of the PVN neurons were investigated.MethodsIn anesthetized rats, extracellular single-unit recording was carried out in vivo on a PowerLab data acquisition system. The renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were recorded. The CSAR was evaluated by the RSNA response to epicardial application of capsaicin. The coordinates for PVN were determined in a stereotaxic instrument according to the Paxinos and Watson rat atlas.1. The effects of epicardial application of saline, capsaicin, bradykinin, adenosine or H2O2 on the activity of the PVN neurons were investigated in rats with baroreceptor denervation and vagotomy. Successive applications of chemicals were separated by at least 15 min for the complete recovery of the neuron discharge and MAP.2. In order to exclude the possibility that the increase of discharge frequency of the PVN neurons was secondary to the elevation of arterial pressure induced by epicardial application of the chemicals, the response of PVN neurons to transient and mild elevation in MAP induced by the slight aortic coarctation was determined in rats with baroreceptor denervation and vagotomy.3. The effects of epicardial application of capsaicin on the activity of the PVN neurons were determined and compared between rats with baroreceptor denervation and vagotomy and rats without baroreceptor denervation and vagotomy (intact rats).4. The responses of the PVN neuronal discharge, MAP and RSNA to acute myocardial ischemia were determined in rats with baroreceptor denervation and vagotomy. The coronary artery ligation and sham ligation were carried out randomly. ResultA total of 110 spontaneously active neurons were recorded in 42 rats. The data of 6 neurons were excluded because the location of these neurons was out of the PVN. In 104 spontaneously active neurons in the PVN, 31 neurons were identified to be sensitive to the stimulation of the cardiac sympathetic afferents induced by epicardial application of capsaicin (29.8 %), but 5 neurons were inhibited by epicardial application of capsaicin (4.8 %). The remaining 68 neurons showed no response to capsaicin (65.4 %).1. Capsaicin caused an immediate increase in the activity of neurons in the PVN and arterial pressure. Epicardial application of capsaicin increased the PVN neuronal activity 95.5% and MAP 7.5±1.1 mm Hg. There was no significant difference in the responses of the PVN neuronal activity and MAP between the first and the second application of capsaicin. Epicardial application of bradykinin, adenosine or H2O2 caused similar increases in the PVN neuronal activity and MAP to application of capsaicin.2. Both epicardial application of capsaicin and slight aortic coarctation caused similar increase in MAP. Epicardial application of capsaicin significantly increased the PVN neuronal firing, but slight aortic coarctation had no significant effect on the PVN neuronal firing.3. The increases in the PVN neuronal discharge rate and MAP caused by epicardial application of capsaicin were much less in intact rats than the rats underwent baroreceptor denervation and vagotomy. 4. The PVN neuronal discharge rate increase 103.1% and the RSNA increased by 22.5% during myocardial ischemia, but the MAP had no significant change.Conclusions1. Stimulation of cardiac sympathetic afferents activates the neurons in the PVN. 2. The activity of these neurons in the PVN and the CSAR are reduced by the afferent activities of vagi and baroreceptor.3. Acute myocardial ischemia activates the PVN neurons and causes enhanced sympathetic outflow.