Abstract

Cardiac reflexes originating from sensory receptors in the heart ensure blood supply to vital tissues and organs in the face of constantly changing demands. Atrial volume receptors are mechanically sensitive vagal afferents which relay to the medulla and hypothalamus, affecting vasopressin release and renal sympathetic activity. To date, two anatomically distinct sensory endings have been identified which may subserve cardiac mechanosensation: end‐nets and flower‐spray endings. To map the distribution of atrial receptors in the subendocardial space, we have double‐labelled rat right atrial whole mounts for neurofilament heavy chain (NFH) and synaptic vesicle protein 2 (SV2) and generated high‐resolution maps of the rat subendocardial neural plexus at the cavo‐atrial region. In order to elucidate the nature of these fibres, double labelling with synaptophysin (SYN) and either NFH, calcitonin gene‐related peptide (CGRP), choline acetyltransferase (ChAT) or tyrosine hydroxylase (TH) was performed. The findings show that subendocardial nerve nets are denser at the superior cavo‐atrial junction than the mid‐atrial region. Adluminal plexuses had the finest diameters and stained positively for synaptic vesicles (SV2 and SYN), CGRP and TH. These plexuses may represent sympathetic post‐ganglionic fibres and/or sensory afferents. The latter are candidate substrates for type B volume receptors which are excited by stretch during atrial filling. Deeper nerve fibres appeared coarser and may be cholinergic (positive staining for ChAT). Flower‐spray endings were never observed using immunohistochemistry but were delineated clearly with the intravital stain methylene blue. We suggest that differing nerve fibre structures form the basis by which atrial deformation and hence atrial filling is reflected to the brain.

Highlights

  • Important cardiac reflexes help to ensure that the blood supply to all tissues and organs is maintained in the face of constantly changing demands

  • Whilst SYN, calcitonin gene-related peptide (CGRP), neurofilament heavy chain (NFH) and synaptic vesicle protein 2 (SV2) have labelled fibres, it cannot be stated with certainty that the observed neuronal structures are truly sensory even if they resemble the end-net as described in the literature

  • In the right cavo-atrial junction we have shown that the SYN-labelled terminals in the endocardium (Shenton and Pyner, 2014) have a morphology characteristic of sensory endings (Drummond et al, 1998; Maeda et al, 1999)

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Summary

| INTRODUCTION

Important cardiac reflexes help to ensure that the blood supply to all tissues and organs is maintained in the face of constantly changing demands. Two anatomically distinct nerve endings have been described as candidate sensory specialisations for atrial receptors: end-nets and complex unencapsulated endings (diffuse and compact) or flower-sprays. The end-net structure has been described as distinct from that of the complex unencapsulated end organs (Coleridge et al, 1957; Holmes, 1957a; 1957b; 1958) and suggests this structure is present in both atrial and ventricular endocardium but more abundant in the atria (Miller and Kasahara, 1964). The observation that end-net distribution is more extensive throughout the atrial endocardium than the complex unencapsulated nerve endings (Coleridge et al, 1957; Holmes, 1957b) may be important in terms of signalling atrial function to the brain. Findings relating to NFH/SV2 double labelling have been presented in preliminary form at the Physiological Society annual conference – Proc Physiol Soc 43 (2019) C102

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