Elsevier

Brain Research

Volume 753, Issue 1, 4 April 1997, Pages 102-119
Brain Research

Research report
Fos induction in central structures after afferent renal nerve stimulation

https://doi.org/10.1016/S0006-8993(96)01497-7Get rights and content

Abstract

Experiments were done in the conscious and unrestrained rat to identify central structures activated by electrical stimulation of afferent renal nerves (ARN) using the immunohistochemical detection of Fos-like proteins. Fos-labelled neurons were found in a number of forebrain and brainstem structures bilaterally, but with a contralateral predominance. Additionally, Fos-labelled neurons were found in the lower thoracolumbar spinal cord predominantly ipsilateral to the side of ARN stimulation. Within the forebrain, neurons containing Fos-like immunoreactivity after ARN stimulation were primarily found along the outer edge of the rostral organum vasculosum of the laminae terminalis, in the medial regions of the subfornical organ, in the median preoptic nucleus, in the ventral subdivision of the bed nucleus of the stria terminalis, along the lateral part of the central nucleus of the amygdala, throughout the deeper layers of the dysgranular insular cortex, in the parvocellular component of the paraventricular nucleus of the hypothalamus (PVH), and in the paraventricular nucleus of the thalamus. Additionally, a smaller number of Fos-labelled neurons was observed in the supraoptic nucleus, in the magnocellular component of the PVH and along the lateral border of the arcuate nucleus. Within the brainstem, Fos-labelled neurons were found predominantly in the commissural and medial subnuclei of the nucleus of the solitary tract and in the external subnucleus of the lateral parabrachial nucleus. A smaller number were observed near the caudal pole of the locus coeruleus, and scattered throughout the ventrolateral medullary and pontine reticular formation in the regions known to contain the A1, C1 and A5 catecholamine cell groups. The final area observed to contain Fos-labelled neurons in the central nervous system was the thoracolumbar spinal cord (T9–L1) which contained cells in laminae I–V of the dorsal horn ipsilateral to side of stimulation and in the intermediolateral cell column at the same levels bilaterally, but with an ipsilateral predominance. Few, if any Fos-labelled neurons were observed in the same structures of control animals in which the ARN were stimulated, but the renal nerves proximal to the site of stimulation were transected, or in the sham operated animals. These data indicate that ARN information originating in renal receptors is conveyed to a number of central areas known to be involved in the regulation of body fluid balance and arterial pressure, and suggest that this afferent information is an important component of central mechanisms regulating these homeostatic functions. © 1997 Elsevier Science B.V. All rights reserved.

Introduction

It is now well accepted that the kidney is innervated by both efferent and afferent renal nerve fibers (for a review see 6, 34). The efferent renal innervation is composed of postganglionic sympathetic fibers [37]that exert influences on renin release, renal hemodynamics, and the tubular reabsorption of water and sodium [27]. The afferent innervation is not involved directly in the regulation of vascular or tubular function within the kidney, but plays an important role in the reflex regulation of these functions 27, 57, 80, 119, 120.

The kidney has been shown to contain at least two groups of receptors, renal mechanoreceptors and chemoreceptors (for a review see 119, 120). The renal mechanoreceptors have been divided into two functional groups: those that are and those that are not tonically active, both of which are activated by changes in arterial, venous and ureteral pressures 83, 123. The renal chemoreceptors have also been divided into two functional groups; R1 receptors are silent and respond to prolonged ischemia, whereas R2 receptors are spontaneously active and respond to renal ischemia, and concentrated urine and changes in the ionic composition of the renal interstitium 94, 95, 96. Finally, there is some evidence to suggest that the kidney also contains natrio-receptors 71, 102and possibly nociceptors [26]. The information conveyed by afferent renal nerves is thought to be involved in cardiovascular regulation and body fluid homeostasis as stimulation of ARN elicits renorenal reflexes 10, 11that lead to changes in systemic arterial pressure 14, 91, 115and vasopressin release 14, 115. In addition, experimental evidence exits that suggests that ARN may play an important role in the establishment and maintenance of hypertension in several different experimental models of the disease 53, 57, 58, 59, 88, 114, 129.

Information from these renal receptors has been shown using electrophysiological techniques to be relayed to several different levels of the neuraxis 1, 2, 3, 4, 8, 17, 20, 60, 61, 124, 125. However, a systematic analysis of the central projections of ARN has not been done. This likely reflects the fact that it is not experimentally feasible to systematically explore the complete nervous system using electrophysiological methods to investigate central areas that receive and integrate ARN information. However, recent studies have used the immunohistochemical detection of the protooncogene c-Fos and of Fos-like proteins in neurons as an indicator of neuronal activation and has allowed the identification of the neuronal system activated by a specific stimulus 28, 106, 111, 112. In particular, this technique has been widely used to identify central pathways that may play a role in the regulation of the cardiovascular system 31, 67, 77and in the control of body fluid balance 46, 47, 48, 49, 50, 76, 85, 111. Therefore, the present study was done to identify central structures that were activated following electrical stimulation of ARN in the awake, unrestrained rat using the immunohistochemical detection of the Fos-like proteins.

Section snippets

Isolation and stimulation of ARN

Experiments were done in 17 male Wistar rats weighing 250–350 g. Approximately 20–36 h prior to the experiments the animals were anesthetized using chloral hydrate (400 mg/kg, i.p.) and a lateral laparotomy was performed to expose the left kidney. Under a stereoscopic dissection microscope, the left renal nerves were isolated using blunt dissection with glass rods, identified as they emerged from the hilus of the kidney, cleaned of connective and fat tissue, and separated from the renal artery.

Results

Central structures that consistently contained Fos-labelled neurons in the forebrain, brainstem and spinal cord after ARN stimulation will be described in this report. Altering the pattern or frequency of stimulation did not change the distribution of Fos-labelled neurons within the central nervous system. Few, if any Fos-labelled neurons were observed in the sham operated animals or in the animals in which the renal nerves were stimulated, but the renal nerves proximal to the stimulating

Discussion

The immunohistochemical detection of c-Fos and Fos-related proteins in neurons has been widely used as a method to identify neuronal systems that are activated by specific sensory stimulation 30, 31, 55, 67, 72, 77, 87, 93. This study has provided immunohistochemical evidence of central structures that increased their activity in response to stimulation of ARN in the conscious, unrestrained rat. As the ARN are known to convey information from renal mechanoreceptors and chemoreceptors, these

Acknowledgements

This work was supported by the Heart and Stroke Foundation of Ontario.

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