Hypotension and short‐term anaesthesia induce ERK1/2 phosphorylation in autonomic nuclei of the brainstem

Abstract

The aims of this study were: first, to investigate the effects of anaesthesia on phosphorylated extracellular signal-regulated kinase (p-ERK)1/2-immunoreactivity (-ir) in the brainstem; second, to choose the best anaesthetic for p-ERK1/2 studies; and third, to determine the effect of short-term hypotension on p-ERK1/2-ir in the brainstem. Rats were anaesthetized with halothane, sodium pentobarbital or 100% CO2 narcosis, or were cervically dislocated and within 5 min perfused and the brains processed immunohistochemically for pERK1/2-ir. p-ERK1/2-ir was primarily observed in regions associated with cardiovascular and/or respiratory control. Several regions consistently showed dense p-ERK1/2 labelling, including a restricted region of the ventrolateral medulla (VLM). In contrast, other regions showed differential labelling depending on the mode of death. Cervical dislocation showed the least VLM labelling, limited to a discrete area approximately 0.6-1.4 mm caudal to the facial nucleus. Anaesthetics induced labelling throughout the VLM, with halothane inducing the most. Many p-ERK1/2-ir VLM neurons were catecholaminergic following halothane or sodium pentobarbital anaesthesia, but no double labelling was seen following cervical dislocation. Of the anaesthetics, sodium pentobarbital induced the least labelling and was used subsequently. Intravenous hydralazine was used to induce a 20-min period of hypotension, whereas arterial pressure did not change in vehicle-treated animals. Hydralazine evoked more pERK-ir neurons in specific regions, including the VLM, nucleus tractus solitarius (NTS), parabrachial nuclei, Kolliker-Fuse nucleus and locus coeruleus. Approximately twice as many p-ERK1/2-positive neurons were seen in the intermediate NTS and rostral VLM following hydralazine compared with the vehicle. In conclusion, p-ERK1/2-ir identifies neurons in central autonomic regions, and their number and distribution are markedly affected by anaesthetics, and are increased in some regions by short-term hypotension.

Brainstem Phosphorylated Extracellular Signal-Regulated Kinase 1/2-Nitric-Oxide Synthase Signaling Mediates the Adenosine A2A-Dependent Hypotensive Action of Clonidine in Conscious Aortic Barodenervated Rats

“…In the RVLM, pERK1/2 is implicated in decreases or increases in blood pressure, depending on the experimental conditions and the preparation used (Seyedabadi et al, 2001;Springell et al, 2005;Zhang and Abdel-Rahman, 2005). In cell culture studies, A 2A R activation leads to This study was supported in part by National Institutes of Health Grant 2R01 AA07839.…”

“…These findings, which established a link between the molecular targets for clonidine, ␣ 2A R, and/or I 1 receptor, and central adenosine receptor signaling, are consistent with the physiological role of central A 2A R. It is noteworthy that in the RVLM, the major neuroanatomical target of clonidine, activation of the adenosine A 2A R causes hypotension (Thomas et al, 2000). However, the cellular mechanism implicated in the hypotension mediated by the activation of central adenosine A 2A R has not been investigated.In the RVLM, pERK1/2 is implicated in decreases or increases in blood pressure, depending on the experimental conditions and the preparation used (Seyedabadi et al, 2001;Springell et al, 2005;Zhang and Abdel-Rahman, 2005). In cell culture studies, A 2A R activation leads to This study was supported in part by National Institutes of Health Grant 2R01 AA07839.…”

“…Furthermore, the mechanism by which pERK1/2 generation in the RVLM leads to hypotension is not known. It is imperative to note that 1) pERK1/2 is formed within minutes in brainstem nuclei (Springell et al, 2005), and cell culture studies show that pERK1/2 enhances NOS-NO signaling (Wyatt et al, 2002;Vá squez et al, 2004); and 2) NO generation in the brainstem nuclei causes reduction in blood pressure (Chan et al, 2001). Whether pERK1/2 activation of NOS-NO signaling occurs in vivo and contributes to a biological response has not been investigated.…”

“…In the RVLM, pERK1/2 is implicated in decreases or increases in blood pressure, depending on the experimental conditions and the preparation used (Seyedabadi et al, 2001;Springell et al, 2005;Zhang and Abdel-Rahman, 2005). In cell culture studies, A 2A R activation leads to pERK1/2 generation (Schulte and Fredholm, 2003), and clonidine-like drugs, whose hypotensive action is dependent on central adenosine A 2A R (Nassar and Abdel-Rahman, 2006a,b), enhance the production of pERK1/2 in the RVLM (Zhang and Abdel-Rahman, 2005).…”

The VR1-Positive Primary Afferent-Mediated Expression of pERK in the Lumbosacral Neurons in Response to Mechanical and Chemical Stimulation of the Urinary Bladder in Rats

“…First, the specificity of pERK is higher than cFos. cFos is expressed in a population of cells in spinal cord without any noxious stimulus and thus the response have to be assessed by quantitative comparison while baseline expression of pERK in spinal cord is negligible except in a few cells in SPN which is possible related with anesthesia 32) , Second, since pERK stains the entire perikaryon, it can provide further detailed anatomical information of the activated neurons including synapse with other neurons while cFos stains only nuclei. In our study, the physical and chemical stimulations of the bladder induced the expression of pERK in the lamina I, lamina V, SPN, MDH and DCG in spine, which is in agreement with the result of previous studies.…”