Hemorrhage activates proopiomelanocortin neurons in the rat hypothalamus.
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 beta-endorphin immunoreactive neurons significantly. The proportion of beta-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 microl) 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.
Göktalay
Gökhan
G
Department of Basic and Pharmaceutical Sciences, Albany College of Pharmacy, Union University, 106 New Scotland Avenue, Albany, NY 12208-3492, USA.
Cavun
Sinan
S
Levendusky
Mark C
MC
Resch
Garth E
GE
Veno
Patricia A
PA
Millington
William R
WR
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D001919:Bradycardia / Q000209:etiology / Q000517:prevention & control; D006470:Hemorrhage / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D007022:Hypotension / Q000209:etiology / Q000517:prevention & control; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology*; D007033:Hypothalamus, Middle / Q000378:metabolism; D007150:Immunohistochemistry; D007267:Injections; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D001615:beta-Endorphin / Q000378:metabolism
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D008012:Lidocaine