Enhanced Expression of Cardiac Nerve Growth Factor and Nerve Sprouting Markers in Rats Following Gastric Perforation

Abstract

Endotoxemia and/or systemic inflammation may lead to disturbances in the cardiac autonomic nervous system and consequent arrhythmia. The underlying mechanism remains unclear. Therefore, we investigated the expression of nerve growth factor (NGF) and its association with cardiac sympathovagal balance in a rodent model of self-limited peritonitis. Male Wistar rats were randomized into the following groups: normal control, sham, gastric perforation (GP), and GP treated with methylprednisolone. Cardiac expression of NGF, growth-associated protein 43 (GAP43), along with other nerve markers were evaluated at several time points (6 h to 2 weeks) after GP. An autoregressive process was performed on each detrended electrocardiogram to calculate the heart rate power spectrum. Compared with the normal control and sham groups, expression of NGF was significantly elevated for 1 week after GP. We also found the up-regulated GAP43 and tyrosine hydroxylase protein levels in the GP group, which persisted after recovery from peritonitis. Gastric perforation caused a biphasic change in the ratio of low-frequency to high-frequency power (an index of sympathovagal balance), with an initial decrease followed by recovery at 24 h. Increased NGF and cardiac sympathetic marker expression were temporally associated with the restoration of the cardiac sympathovagal balance. Methylprednisolone abrogated the NGF up-regulation induced by GP and delayed the resumption of sympathovagal balance. We conclude that GP resulted in up-regulation of cardiac NGF, GAP43, and tyrosine hydroxylase expression that coincided with recovery of cardiac sympathovagal balance. Moreover, methylprednisolone can effectively block GP-induced NGF up-regulation.

Metoprolol-Mediated Amelioration of Sympathetic Nerve Sprouting after Myocardial Infarction

“…Growing evidence showed that increased local or systemic inflammation is responsible for cardiac sympathetic hyperinnervation by upregulating NGF expression [9,26]. NGF, a potent neural chemoattractant, plays critical roles in the differentiation, survival, growth and synaptic activity of the sympathetic nervous system [27].…”

“…MI-induced inflammation upregulates nerve growth factor (NGF), which is critical for sympathetic sprouting and is spatiotemporally consistent with sympathetic hyperinnervation [9,10]. Thus, the inflammatory response after MI contributes to sympathetic nerve sprouting.…”

Enhanced Aortic Nerve Growth Factor Expression and Nerve Sprouting in Rats Following Gastric Perforation

“…NGF is expressed by rodent aortic smooth muscle cells (SMCs), rodent arterial SMCs, and human SMCs [5,6]. Several previous studies have suggested the potential role of NGF as a modulator of inflammatory processes [7][8][9][10]. NGF has shown to be up-regulated in inflamed tissues, such as the urinary bladder in cystitis, and mediates inflammatory pain [9].…”

“…Interestingly, NGF expression is induced not only by ''local'' inflammation but also ''remote'' inflammation. Using a rodent model of gastric perforation (GP), we previously demonstrated that self-limited peritonitis results in up-regulation of cardiac NGF and nerve sprouting markers [10]; however, little is known whether aortic NGF expression would also be up-regulated.…”

“…The purpose of this study was to investigate changes in aortic NGF expression after GP, which induced a self-limited peritonitis of 1 wk duration in rats [10]. To further clarify the role of inflammation in NGF expression, methylprednisolone was used in rats with GP as an anti-inflammatory therapy.…”