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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

Li Xia, FAN Ming-Xin, LI Liang, WANG Jin, SHEN Lin-Lin, CAO Yin-Xiang, ZHU Da-Nian, HONG Zhen

Department of Internal Neurology, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China； The Center of Drug Development, Chongqing Technology and Business University, Chongqing 400067, China； School of Public Health, University of South China, Hengyang 421001, China； Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, Shanghai 200032, China

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 ΔAP and ΔHR 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 ΔAP and ΔHR. 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.

Key words: Rostral ventrolateral medulla; dorsal periaquaductal gray of midbrain; adrenomedullin; stress; heart rate; artery pressure; adrenomedullin receptor antagonist; rat

Received: 2009-01-16　　Accepted: 2009-05-22

Corresponding author: 朱大年　　E-mail: dnzhu@shmu.edu.cn

Citing This Article：

Li Xia, FAN Ming-Xin, LI Liang, WANG Jin, SHEN Lin-Lin, CAO Yin-Xiang, ZHU Da-Nian, HONG Zhen. 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. Acta Physiol Sin 2009; 61 (4): 347-355 (in Chinese with English abstract).