Background:
The paraventricular nucleus (PVN) of the hypothalamus has been identified as a key site involved in sympathoexcitation in chronic heart failure (HF). The aim of this study was to determine whether changes in regulation of reactive oxygen species (ROS) in the PVN are associated with elevations in sympathetic activity early in the development of HF.
Methods:
Renal sympathetic nerve activity and arterial pressure were measured continuously via telemetry both before and after myocardial infarction (MI: ligation of the left anterior descending coronary artery) or sham surgery in male Wistar rats. At 3 weeks post MI animals were perfuse fixed and immunohistochemistry used to determine the expression of enzymes involved in ROS regulation (SOD, NOX4) and nNos within the PVN.
Results:
At 3 weeks post-MI fractional shortening of the left ventricle was 201% in the HF group vs 484% in shams, P<0.05. Post-MI renal sympathetic nerve activity levels showed gradual increases with time, doubling by day 14. Within the PVN significantly fewer neurons were found to be SOD positive in HF vs. sham animals. In contrast, significantly more NOX4 positive neurons were found in HF vs. sham animals. No difference in the number of nNOS expressing neurons was found between groups.
Conclusion:
These findings indicate sympathoexcitation in the development of heart failure is associated with elevated ROS levels within the PVN, both as a consequence of an upregulation of production, via NOX4 and impaired ability to scavenge ROS, via SOD. In contrast, nNOS expression is independent of the sympathoexcitation.