Autonomic nervous system (ANS) dysfunction exacerbates inflammation in dextran sulfate (DSS) model of ulcerative colitis

The autonomic nervous system (ANS) plays an important role in modulating ones response to stress. We have previously demonstrated in the stress reactivation model of colitis that pretreatment with hexamethonium, a nicotinic ganglionic blocking agent, prevents stress-induced reactivation colitis. In this study we assessed neurocardiac response to stress. Biopotential transmitters were surgically implanted subcutaneously, for later recording of ECG' s in conscious rats. Once rats had recovered (~l week), intrarectal (ir) dinitrobenzene sulfonic acid (DNB), 20 mg dissolved in 250 J.Ll 40% ethanol was administered. Six weeks later rats were subjected to 3hr restraint stress (RS). Twenty-min ECG recordings were taken at 5 min, 2hr into the stress and 30 min post stress. Heart rate variability as measured from the ECG's was subjected to power spectral analysis and low frequency (LF. predominantly sympathetic) and high frequency (HF, predominantly parasympathetic) spectrums determined. One hr post stress rats received ir DNB, 20 mg dissolved in 250 J.Ll saline. Two days later the rats were sacrificed and their colons examined. At 5 minutes into the stress rats demonstrated a strong sympathetic response indicated by a significant increase in heart rate (295.7 ± 2.2 to 444.4 ± 16.5 beats/min), LF power (433.6 ± 6.9 to 487 ± 3.1 ms") and LF:HF ratio(6.2 ± 0.8 to 27.9 ± 4.5). This increase in sympathetic activity was still evident at 2 hr into the stress. Thirty minutes post stress rats demonstrated a rebound increase in parasympathetic activity indicated by an increase in HF power (76.3 ± 7.1 at baseline, 20.6 ± 2.7 at 5 min RS, 129.4 ± 23.3 ms? post RS) and a decrease in LF power to 380.2 ± 23.0 ms and in the LF:HF ratio to 4.1 ± 0.98. Macroscopic examination of the colons revealed gross ulceration with an average macroscopic damage score of 4(range 3-5). Microscopic examination revealed marked mucosal disruption with loss of epithelium, profound hyperemia, and marked infiltration by neutrophils, macrophages, lymphocytes and eosinophils. This study demonstrated the ANS response to stress, causing colitic relapse, characterized by sympathetic activation followed by rebound parasympathetic activation. These data suggest that changes in sympathovagal balance are important in the stress response and further understanding of these responses will likely lead to new and novel therapies directed at preventing stress induced relapses of IBD. Supported by CAGIMRC Canada