Effects of hypocretin and norepinephrine interaction in bed nucleus of the stria terminalis on arterial pressure.
Forebrain neuronal circuits containing hypocretin-1 (hcrt-1) and norepinephrine (NE) are important components of central arousal-related processes. Recently, these two systems have been shown to have an overlapping distribution within the bed nucleus of the stria terminalis (BST), a limbic structure activated by stressful challenges, and which functions to adjust arterial pressure (AP) and heart rate (HR) to the stressor. However, whether hcrt-1 and NE interact in BST to alter cardiovascular function is unknown. Experiments were done in urethane-α-chloralose anesthetized, paralyzed, and artificially ventilated male Wistar rats to investigate the effect of hcrt-1 and NE on the cardiovascular responses elicited by l-glutamate (Glu) stimulation of BST neurons. Microinjections of hcrt-1, NE or tyramine into BST attenuated the decrease in AP and HR to Glu stimulation of BST. Additionally, combined injections of hcrt-1 with NE or tyramine did not elicit a greater attenuation than either compound alone. Furthermore, injections into BST of the α2-adrenergic receptor (α2-AR) antagonist yohimbine, but not the α1-AR antagonist 2-{[β-(4-hydroxyphenyl)ethyl]aminomethyl}-1-tetralone hydrochloride, blocked both the hcrt-1 and NE-induced inhibition of the BST cardiovascular depressors responses. Finally, injections into BST of the GABAA receptor antagonist bicuculline, but not the GABAB receptor antagonist phaclofen, blocked the hcrt-1 and NE attenuation of the BST Glu-induced depressor and bradycardia responses. These data suggest that hcrt-1 effects in BST are mediated by NE neurons, and hcrt-1 likely acts to facilitate the synaptic release of NE. NE neurons, acting through α2-AR may activate Gabaergic neurons in BST, which in turn through the activation of GABAA receptors inhibit a BST sympathoinhibitory pathway. Taken together, these data suggest that hcrt-1 pathways to BST through their interaction with NE and Gabaergic neurons may function in the coordination of cardiovascular responses associated with different behavioral states.
Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada. Electronic address: john.ciriello@schulich.uwo.ca.
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D000818:Animals; D062186:Arterial Pressure / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009434:Neural Pathways / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D000068797:Orexins; D051381:Rats; D017208:Rats, Wistar; D012686:Septal Nuclei / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D009638:Norepinephrine
2-{[β-(4-hydroxyphenyl)ethyl]aminome thyl}-1-tetralone hydrochloride; 3rd ventricle; A1/A2/A5; AMB; AMG; AP; AR; BIC; BST; CVLM; GABA; GABA(A)-receptor antagonist bicuculline methiodide; Glu; HEAT hydrochloride; HR; IML; LH; LPO; LS; MAP; MPN; MS; NE; RVLM; SF; SI; SNS; V3; VL; VN; ac; adrenergic receptor; adrenergic receptors; amygdala; anterior commissure; arterial pressure; bed nucleus of the stria terminalis; brainstem noradrenergic/norepinephrine cell groups; cardiovascular regulation; caudal ventrolateral medulla; cc; corpus callosum; extended amygdala; fornix; fx; hcrt-1; heart rate; hypocretin-1; int; intermediolateral cell column; internal capsule; l-glutamate; lateral hypothalamus; lateral preoptic area; lateral septum; lateral ventricle; mean arterial pressure; medial preoptic nucleus; medial septum; norepinephrine/noradrenaline; nucleus ambiguus; oc; optic chiasma; orexin; rostral ventrolateral medulla; septofimbrial nucleus; st; stress; stria terminalis; substantia innominata; sympathetic nervous system; vagus nerve