Nickel-regulated heart rate variability: The roles of oxidative stress and inflammation

Heart rate variability (HRV) has been reported to be a putative marker of cardiac autonomic imbalance caused by exposure to ambient particulate matter (PM). Our objective in this study was to determine the effects on HRV from exposure to nickel, an important chemical component of ambient PM that results in oxidative stress and inflammation. HRV data were collected for 72h before lung exposure (baseline) and 72h after intratracheal exposure (response) to nickel sulphate (NiSO₄; 526μg) in Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats. The antioxidant N-acetyl-l-cysteine (NAC) and the anti-inflammatory celecoxib were intraperitoneally injected to examine post-exposure oxidative and inflammatory responses. Self-controlled experiments examined the effects of NiSO₄ exposure on average normal-to-normal intervals (ANN), natural logarithm-transformed standard deviation of the normal-to-normal intervals (LnSDNN) and root mean square of successive differences of adjacent normal-to-normal intervals (LnRMSSD); the resulting data were sequentially analysed using the generalised estimating equation model. HRV effects on NiSO₄-exposed SH rats were greater than those on NiSO₄-exposed WKY rats. After adjusted the HRV responses in the WKY rats as control, ANN and LnRMSSD were found to be quadratically increased over 72h after exposure to NiSO₄. Both NAC and celecoxib mitigated the NiSO₄-induced alterations in HRV during the exposure period. The results suggest that concurrent Ni-induced oxidative stress and inflammatory responses play important roles in regulating HRV. These findings help bridge the gap between epidemiological and clinical studies on the plausible mechanisms of the cardiovascular consequences induced by chemical components in ambient PM.