Introduction subsequently involve inhibitory neurons in the caudal

Brain Research 887 2000 46–52 www.elsevier.com locate bres Research report Responses of adrenal sympathetic preganglionic neurons to stimulation of cardiopulmonary receptors Wei-Hua Cao, Shaun F. Morrison Department of Physiology , Northwestern University Medical School, Chicago, IL 60611, USA Accepted 12 September 2000 Abstract The current study examined whether or not the activation of Bezold-Jarisch reflex with administration of phenylbiguanide PBG, 100 mg kg into right atrium elicits differential responses in the two populations of adrenal sympathetic preganglionic neurons SPNs regulating the release of epinephrine EPI ADR SPNs and norepinephrine NE ADR SPNs, respectively, from adrenal medullary chromaffin cells. Extracellular activity of 48 adrenal SPNs in the intermediolateral cell column IML were recorded in urethane chloralose-anesthetized rats. Twenty-three EPI ADR SPNs and 25 NE ADR SPNs were antidromically activated by stimulation of left adrenal nerve and orthodromically activated by rostral ventrolateral medulla RVLM stimulation. At a mean arterial pressure MAP of 99.662.8 mmHg, the mean spontaneous discharge rates of EPI ADR SPNs and NE ADR SPNs were 6.260.5 and 4.360.5 spikes s, respectively. Intra-atrial PBG markedly inhibited 96 of EPI ADR SPNs by 3.860.4 spikes s; n522 and 76 of NE ADR SPNs by 2.960.5 spikes s; n519 with hypotensive responses DMAP533.265.3 and 26.465.0 mmHg, respectively. The remaining SPNs were weakly excited or unaffected. We conclude that both groups of SPNs regulating catecholamine release are primarily inhibited by stimulation of cardiopulmonary receptors and that these responses parallel the sympathoinhibitory and hypotensive components of the Bezold-Jarisch reflex.  2000 Elsevier Science B.V. All rights reserved. Theme : Endocrine and autonomic regulation Topic : Cardiovascular regulation Keywords : Phenylbiguanide; Epinephrine; Bezold-Jarisch reflex; Sympathoinhibition; Intermediolateral cell column; Rostral ventrolateral medulla

1. Introduction subsequently involve inhibitory neurons in the caudal

ventrolateral medulla CVLM, projecting to the rostral Activation of cardiopulmonary, chemosensitive vagal ventrolateral medulla RVLM [7,25,27,28]. While these afferent C-fibers ending in the lungs and heart, by injection data suggest a pathway similar to that of the baroreceptor of chemical substances such as veratrum alkaloids, reflex [25,27,28], the central integration mechanisms un- serotonin, phenylbiguanide PBG or capsaicin, causes a derlying the Bezold-Jarisch reflex are less well understood. profound bradycardia, hypotension and apnoea [14,24]. The demonstration that stimulation of chemosensitive These responses, first described by von Bezold and Hirt in cardiac vagal afferents by phenyldiguanide decreased renal 1867 and involving receptors characterized by Jarisch and sympathetic nerve activity SNA, but increased adrenal Zotterman in 1948 [11], are referred to as the Bezold- SNA [9], suggests that the sympathetic outflow to the Jarisch reflex [6,13,14,24]. Bezold-Jarisch reflex responses adrenal gland may be an exception to the general finding are mediated by neurons in the nucleus tractus solitarii that Bezold-Jarisch reflex responses are sympatho- NTS that receive input from vagal primary afferents, inhibitory. To test this possibility and to determine if the originating in the heart and lungs [3,12,15,16], and may phenyldiguanide-evoked increase arose from pre- or post- ganglionic axons in the adrenal nerve, we recorded the responses of adrenal SPNs to activation of the Bezold- Corresponding author. Tel.: 11-312-503-5024; fax: 11-312-503- Jarisch reflex with right atrial administration of PBG. 5101. E-mail address : s-morrison2northwestern.edu S.F. Morrison. Recently, adrenal sympathetic preganglionic neurons 0006-8993 00 – see front matter  2000 Elsevier Science B.V. All rights reserved. P I I : S 0 0 0 6 - 8 9 9 3 0 0 0 2 9 6 4 - 4 W .-H. Cao, S.F. Morrison Brain Research 887 2000 46 –52 47 SPNs have been divided into two physiologically distinct effect. The position of the atrial catheter was verified after populations: EPI ADR SPNs, which putatively regulate the each experiment. activity of adrenal epinephrine-secreting chromaffin cells, and NE ADR SPNs that control adrenal norepinephrine- 2.3. Recording and identification of adrenal sympathetic secreting chromaffin cells [17]. In the present study, we preganglionic neurons distinguished between these two groups of adrenal SPNs to ascertain if PBG might evoke differential responses in The extracellular action potentials of adrenal SPNs were those regulating adrenal epinephrine secretion and those recorded with glass pipettes containing an electropho- controlling norepinephrine release. The results suggest that retically sharpened 7-mm-diameter carbon filament. The the cardiopulmonary receptors activated by intra-atrial reference electrode was inserted into muscle lateral to the PBG evoke a uniform inhibition of adrenal SPNs. A vertebral column or lateral to the occipital bone. Spinal preliminary report of these results has been published [4]. penetrations were made along the dorsal root entry zone, and adrenal SPNs were located 0.7–1.1 mm below the dorsal surface. Neuronal signals were amplified, filtered

2. Materials and methods