Abstract
BackgroundCardiac sympathetic afferent reflex (CSAR) is a positive-feedback, sympathoexcitatory reflex. Paraventricular nucleus (PVN) is an important component of the central neurocircuitry of the CSAR. The present study is designed to determine whether endothelin-1 (ET-1) in the PVN modulates the CSAR and sympathetic activity, and whether superoxide anions are involved in modulating the effects of ET-1 in the PVN in rats.Methodology/Principal FindingsIn anaesthetized Sprague–Dawley rats with cervical vagotomy and sinoaortic denervation, renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. The CSAR was evaluated by the responses of the RSNA and MAP to epicardial application of capsaicin. Microinjection of ET-1 into the bilateral PVN dose-dependently enhanced the CSAR, increased the baseline RSNA and MAP. The effects of ET-1 were blocked by PVN pretreatment with the ETA receptor antagonist BQ-123. However, BQ-123 alone had no significant effects on the CSAR, the baseline RSNA and MAP. Bilateral PVN pretreatment with either superoxide anion scavenger tempol or polyethylene glycol-superoxide dismutase (PEG-SOD) inhibited the effects of ET-1 on the CSAR, RSNA and MAP. Microinjection of ET-1 into the PVN increased the superoxide anion level in the PVN, which was abolished by PVN pretreatment with BQ-123. Epicardial application of capsaicin increased superoxide anion level in PVN which was further enhanced by PVN pretreatment with ET-1.ConclusionsExogenous activation of ETA receptors with ET-1 in the PVN enhances the CSAR, increases RSNA and MAP. Superoxide anions in PVN are involved in the effects of ET-1 in the PVN.
Highlights
Endothelins (ET) are recognized for their function in central regulation of cardiovascular activity [1,2]
In central nervous system (CNS), ET-1 is produced by vascular endothelial cells, neurone and/or non-neural elements or delivered by way of the cerebrospinal fluid [3].It has been reported that injection of ET-1 into the cerebral ventricles evokes a pressor response in rats [4], which is mediated by increased sympathetic outflow [5]
Effects of BQ123 The representative recordings showed that Paraventricular nucleus (PVN) microinjection of ET-1 enhanced the Cardiac sympathetic afferent reflex (CSAR), which was abolished by pretreatment with ETA receptor antagonist BQ123 (Fig. 2)
Summary
Endothelins (ET) are recognized for their function in central regulation of cardiovascular activity [1,2]. Intracerebroventricular injections of ET-1 increases sympathetic nerve activity and blood pressure via ETA receptors but not via ETB receptors in rats [7]. These results suggest that central ET-1 is involved in the modulation of blood pressure and sympathetic output. The response of ET-1 in the baroreflexintact rats is independent from the AVP release [1] These results suggest that the AVP is not the necessary factor in the pressor response to central ET-1. The present study is designed to determine whether endothelin-1 (ET-1) in the PVN modulates the CSAR and sympathetic activity, and whether superoxide anions are involved in modulating the effects of ET-1 in the PVN in rats
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