Research Report Hemorrhage activates proopiomelanocortin neurons in the rat hypothalamus Gökhan Göktalay a,b , Sinan Cavun a,b , Mark C. Levendusky a , Garth E. Resch c , Patricia A. Veno d , William R. Millington a, ⁎ a Department of Basic and Pharmaceutical Sciences, Albany College of Pharmacy, Union University, 106 New Scotland Avenue, Albany, NY 12208-3492, USA b Department of Pharmacology and Clinical Pharmacology, Uludag University Medical Faculty, Bursa, Turkey c Department of Molecular Biology, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64108, USA d Department of Pathology, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA ARTICLE INFO ABSTRACT Article history: Accepted 12 November 2005 Available online 5 January 2006 Severe blood loss lowers arterial pressure through a central mechanism that is thought to include opioid neurons. In this study, we investigated whether hemorrhage activates proopiomelanocortin (POMC) neurons by measuring Fos immunoreactivity and POMC mRNA levels in the medial basal hypothalamus. Hemorrhage (2.2 ml/100 g body weight over 20 min) increased the number of Fos immunoreactive neurons throughout the rostral– caudal extent of the arcuate nucleus, the retrochiasmatic area and the peri-arcuate region lateral to the arcuate nucleus where POMC neurons are located. Double label immunohistochemistry revealed that hemorrhage increased Fos expression by β- endorphin immunoreactive neurons significantly. The proportion of β-endorphin immunoreactive neurons that expressed Fos immunoreactivity increased approximately four-fold, from 11.7 ± 1.4% in sham-operated control animals to 42.0 ± 5.2% in hemorrhaged animals. Hemorrhage also increased POMC mRNA levels in the medial basal hypothalamus significantly, consistent with the hypothesis that blood loss activates POMC neurons. To test whether activation of arcuate neurons contributes to the fall in arterial pressure evoked by hemorrhage, we inhibited neuronal activity in the caudal arcuate nucleus by microinjecting the local anesthetic lidocaine (2%; 0.1 or 0.3 μl) bilaterally 2 min before hemorrhage was initiated. Lidocaine injection inhibited hemorrhagic hypotension and bradycardia significantly although it did not influence arterial pressure or heart rate in non- hemorrhaged rats. These results demonstrate that hemorrhage activates POMC neurons and provide evidence that activation of neurons in the arcuate nucleus plays an important role in the hemodynamic response to hemorrhage. © 2005 Elsevier B.V. All rights reserved. Keywords: Hemorrhage Proopiomelanocortin β-Endorphin c-Fos Blood pressure Arcuate nucleus BRAIN RESEARCH 1070 (2006) 45 – 55 ⁎ Corresponding author. Fax: +1 518 445 7202. E-mail address: millingw@acp.edu (W.R. Millington). 0006-8993/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2005.11.076 available at www.sciencedirect.com www.elsevier.com/locate/brainres