Pattern of neuronal activation in rats with CHF after myocardial infarction

To identify neuronal populations possibly contributing to the sympathetic hyperactivity in rats with congestive heart failure (CHF) after myocardial infarction (MI), immunohistochemical detection of Fra-like immunoreactivity (Fra-LI) was used as a marker of long-term neuronal activation. In adult Wistar rats, 2 and 4 wk after left coronary artery ligation, left ventricular (LV) peak systolic pressure and LV end-diastolic pressure were measured, immediately followed by transcardial perfusion and removal of the heart and brain. The brains were processed using an antibody that recognizes Fos, FosB, Fra-1, and Fra-2 for the detection of Fra-LI and using an antibody that only recognizes Fos-like immunoreactivity (Fos-LI). At both 2 and 4 wk after large MI, LV peak systolic pressure was significantly decreased and LV end-diastolic pressure increased. At 2 wk post-MI or sham surgery, Fra-LI was observed in several areas of either group but was significantly higher in the MI versus the sham group in the magnocellular division of the paraventricular nucleus (PVN), supraoptic nucleus (SON), subfornical organ, and caudal part of the nucleus of the solitary tract. At 4 wk after large MI, Fra-LI was clearly detected in the parvocellular and magnocellular divisions of the PVN, SON, and locus ceruleus. Modest expression was noted in these nuclei in rats with small MI, whereas Fra-like positive immunoreactive neurons were barely detectable in the sham group 4 wk postsurgery. In these nuclei, the extent of expression of Fra-LI correlated significantly with the LV end-diastolic pressure. Fos-LI was only noted in the cerebral cortex. These results indicate clear activation of neurons as identified by Fra-LI in specific cardiovascular control centers in rats with CHF 2 and 4 wk post-MI.