Research reportFos induction in central structures after afferent renal nerve stimulation
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.
References (130)
- Ammons, W.S., Characteristics of spinoreticular and spinothalamic neurons with renal input, J. Neurophysiol., 58 (1987)...
- Ammons, W.S., Renal and somatic input to spinal neurons antidromically activated from the ventrolateral medulla, J....
- Ammons, W.S., Response of primate spinothalamic tract neurons to renal distention, J. Neurophysiol., 62 (1989)...
- Ammons, W.S., Responses of spinoreticular cells to graded increases in renal venous pressure, Am. J. Physiol., 260...
- Armstrong, D.M., Ross, C.A., Pickel, V.M., Joh, T.H. and Reis, D.J., Distribution of dopamine-, noradrenaline-, and...
- Barajas, L., Liu, L. and Powers, K., Anatomy of the renal innervation: intrarenal aspects and ganglia of origin, Can....
- Brody, M.J., O'Neill, T.P. and Porter, J.P., Role of paraventricular and arcuate nuclei in cardiovascular regulation....
- Calaresu, F.R. and Ciriello, J., Renal afferent nerves affect discharge rate of medullary and hypothalamic single units...
- Calaresu, F.R. and Ciriello, J., Altered concentration of catecholamine in the hypothalamus of the rat after renal...
- Calaresu, F.R., Kim, P., Nakamura, H. and Sato, A., Electrophysiological characteristics of renorenal reflexes in the...