title: Adrenomedullin in the rostral ventrolateral medulla is involved in the regulation of cardiovascular component of defensive responses induced by electrical stimulation of dorsal periaquaductal gray of the midbrain.
abstract: In this study, we used techniques of in situ hybridization, immunohistochemistry, electric stimulation of the dorsal periaquaductal gray of the midbrain (dPAG) and microinjection to investigate the changes of preproadrenomedullin (ppADM) gene expression encoding adrenomedullin (ADM) and ADM-like immunoreactivity (ADM-IR) in the medulla oblongata, especially in the rostral ventrolateral medulla (rVLM) of the rats receiving foot-shock and noise stress for 5 d, and the potential role of ADM in cardiovascular component of defense response in the rVLM. The results showed that ppADM mRNA and ADM-IR were widely distributed throughout the medulla oblongata. Highly labeled neurons were found in the ventrolateral reticular nucleus and hypoglossal nucleus. Moderately labeled neurons were seen in the facial, ambiguus, lateral reticular, paragigantocellular reticular, and inferior olivary nuclei. Weak signal was present over neurons of nucleus of the solitary tract. The expression of ppADM mRNA and ADM-IR increased significantly after foot shock and noise stress for 5 d as compared with that in control group (P<0.01). On the other hand, stimulation of the right dPAG raised the artery pressure (AP) rapidly from (116.4+/-8.9) mmHg to (140.0+/-9.8) mmHg, and heart rate (HR) from (378.0+/-7.5) beats/min to (413.0+/-8.2) beats/min, respectively, in the normotensive rats. After unilaterally microinjection of hADM(22-52) (a specific antagonist of ADM receptor, 1 pmol) into the right rVLM of the normotensive rats for 10 min, the rats received the stimulation of the dPAG again. Then we found that the DeltaAP and DeltaHR were lowered significantly within 60 min compared with those without hADM(22-52) application (P<0.05). After unilaterally microinjection of 0.1 pmol rat ADM (rADM) into the rVLM, dPAG stimulation caused no significant changes in DeltaAP and DeltaHR. Our results that foot-shock and noise stress induced significant increases of ppADM mRNA and ADM-IR in the rVLM, and microinjection of ADM receptor antagonist hADM(22-52) into the rVLM partly blocked the cardiovascular component of stress-defensive response induced by stimulation of the dPAG, suggest that ADM in the rVLM might be an important neurotransmitter or neuroregulator in the regulation of cardiovascular function in the stress-related defensive response.
authors.affiliation: Department of Internal Neurology, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Ming-Xin
authors.initials: MX
authors.lastname: Fan
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Shen
authors.forename: Yin-Xiang
authors.initials: YX
authors.lastname: Cao
authors.forename: Da-Nian
authors.initials: DN
authors.lastname: Zhu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Hong
mesh_terms: D053607:Adrenomedullin / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure; D004558:Electric Stimulation; D006339:Heart Rate; D008526:Medulla Oblongata / Q000502:physiology*; D008845:Microinjections; D009474:Neurons / Q000502:physiology; D010487:Periaqueductal Gray / Q000502:physiology*; D011498:Protein Precursors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011498:Protein Precursors; C112034:preproadrenomedullin; D053607:Adrenomedullin