title: Blunted responsiveness of the neuronal activation marker Fos in brainstem cardiovascular nuclei of cirrhotic rats.
abstract: Cardiovascular function in cirrhosis is deranged, with indirect evidence of abnormal central cardiovascular regulation. We aimed to elucidate the role of brainstem cardiovascular nuclei in hemodynamic regulation by examining the protein product, Fos, of the immediate-early gene c-fos, in cirrhotic rats. Cirrhosis was induced by chronic bile duct ligation (BDL) of 25-days duration, while controls underwent a sham operation. To examine the effects of jaundice per se in the absence of cirrhosis, a third group of 5-day BDL rats was also studied. All rats were anesthetized with pentobarbital, and catheters were inserted to measure baseline blood pressure and heart rate. Separate groups were then subjected to volume manipulation by a hypotensive hemorrhage or isotonic saline infusion, or no challenge. Ninety minutes after the volume manipulation, the animals were killed and the medulla sectioned and stained for Fos by immunohistochemisty. The nucleus tractus solitarius (NTS) of the sham-operated unchallenged rats showed scant Fos immunoreactivity (27.8 +/- 3.3 cells), but both hemorrhage and volume infusion significantly increased Fos staining (86.0 +/- 3.7 and 95.2 +/- 8.5, respectively). In contrast, the unchallenged cirrhotic rats showed markedly increased Fos in the NTS (154.6 +/- 27.0), but neither hemorrhage nor volume infusion significantly changed the amount of Fos staining. Fos staining in the ventrolateral medulla (VLM) followed a similar pattern with low staining in the unchallenged sham rats and increased staining in the other groups, but no differences between the unchallenged and the volume-manipulated cirrhotic groups. The 5-day BDL jaundiced rats showed no baseline increase in Fos staining, nor any significant increase after hemorrhage. These results showing baseline activation of central neuronal regions responsible for blood pressure homeostasis, but completely blunted responsiveness in cirrhotic rats, confirm a central origin of disordered cardiovascular regulation. The presence of jaundice may also contribute to the central cardiovascular hyporesponsiveness.
authors.affiliation: Gastroenterology Research Group, University of Calgary, Alberta, Canada.
authors.forename: D R
authors.initials: DR
authors.lastname: Breitman
authors.forename: S S
authors.initials: SS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001810:Blood Volume / Q000502:physiology; D001933:Brain Stem / Q000378:metabolism* / Q000502:physiology; D002319:Cardiovascular System / Q000378:metabolism / Q000503:physiopathology*; D002779:Cholestasis / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate; D007150:Immunohistochemistry; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016760:Proto-Oncogene Proteins c-fos