It has long been suggested that reactive oxygen species (ROS) play a role in oxygen sensing via peripheral chemoreceptors, which would imply their involvement in chemoreflex activation and autonomic regulation of heart rate. We hypothesize that antioxidant affect neurogenic cardiovascular regulation through activation of chemoreflex which results in increased control of sympathetic mechanism regulating heart rhythm. Activity of xanthine oxidase (XO), which is among the major endogenous sources of ROS in the rat has been shown to increase during hypoxia promote oxidative stress. However, the mechanism of how XO inhibition affects neurogenic regulation of heart rhythm is still unclear. The study aimed to evaluate effects of allopurinol-driven inhibition of XO on autonomic heart regulation in rats exposed to hypoxia followed by hyperoxia, using heart rate variability (HRV) analysis. 16 conscious male Wistar rats (350 g): control-untreated (N = 8) and pretreated with Allopurinol-XO inhibitor (5 mg/kg, followed by 50 mg/kg), administered intraperitoneally (N = 8), were exposed to controlled hypobaric hypoxia (1h) in order to activate chemoreflex. The treatment was followed by 1h hyperoxia (chemoreflex suppression). Time-series of 1024 RR-intervals were extracted from 4kHz ECG recording for heart rate variability (HRV) analysis in order to calculate the following time-domain parameters: mean RR interval (RRi), SDNN (standard deviation of all normal NN intervals), rMSSD (square root of the mean of the squares of differences between adjacent NN intervals), frequency-domain parameters (FFT method): TSP (total spectral power) as well as low and high frequency band powers (LF and HF). At the end of experiment we used rat plasma to evaluate enzymatic activity of XO and markers of oxidative stress: protein carbonyl group and 8-isoprostane concentrations. Enzymatic activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measures in erythrocyte lysates. Allopurinol reduced oxidative stress which was the result of hypoxia/hyperoxia, as shown by decreased 8-isoprostane plasma concentration. XO inhibition did not markedly influence HRV parameters in standard normoxia. However, during hypoxia, as well as hyperoxia, allopurinol administration resulted in a significant increase of autonomic control upon the heart as shown by increased SDNN and TSP, with an increased vagal contribution (increased rMSSD and HF), whereas sympathovagal indexes (LF/HF, SDNN/rMSSD) remained unchanged. Observed regulatory effects of XO inhibition did not confirm preliminary hypothesis which suggested that an antioxidant such as allopurinol might activate chemoreflex resulting in augmented sympathetic discharge to the heart. The HRV regulatory profile of XO inhibition observed during hypoxia as well as post-hypoxic hyperoxia corresponds to reported reduced risk of sudden cardiovascular events. Therefore our data provide a new argument for therapeutical use of allopurinol in hypoxic conditions.
16 November 2005 in Journal of Medicinal Chemistry
Continuous positive energy imbalance leads to obesity, which increases the risk of developing non-alcoholic fatty liver disease. The hepatoprotective effect of ethyl pyruvate has been revealed in several studies. Therefore, we examined the effect of ethyl pyruvate supplementation on liver cell damage, metabolism, membrane fluidity, and oxidative stress markers in rats fed a high-fat diet. After 6-wk feeding of a control or high-fat diet, Wistar rats were divided into 4 groups: control diet, control diet and ethyl pyruvate, high-fat diet, and high-fat diet and ethyl pyruvate. Ethyl pyruvate was administered as a 0.3% solution in drinking water, for the following 6 wk. Ethyl pyruvate intake attenuated the increase in activities of plasma transaminases and liver TNF-α. However, the supplementation was without effect in the lipid profiles, membrane fluidity or oxidative metabolism in liver induced by the high-fat diet. Our data confirm the potency of ethyl pyruvate against cell liver damage. Nevertheless, prolonged intake did not affect the development of a fatty liver.
A characteristic feature of the cardiac response to diving is the uncertainty in predicting individual course. The aim of the study was to determine whether resting regulatory heart rate determinants assessed before diving may be predictors of cardiac response in a simulated diving test. The research was conducted with 65 healthy volunteers (37 women and 28 men) with an average age of 21.13 years (20–27 years) and a BMI of 21.49 kg/m2 (16.60–28.98). The simulated diving test consisted of stopping breathing after maximum inhaling and voluntarily immersing the face in water (8–10 °C) for as long as possible. The measurements included heart rate variability (HRV) analysis before diving and determination of the course of the cardiac response to diving—minimum and maximum heart rate (HR). The results indicate that minimum HR during diving (MIN_div) is dependent on the short-term HRV measures, which proves the strong influence of the parasympathetic system on the MIN_div. The lack of dependence of MIN_div on short-term HRV in women may be associated with differences in neurogenic HR regulation in women and men. In conclusion, cardiac response to simulated diving is strictly dependent on the autonomic regulation of the heart rhythm under resting conditions. The course of the cardiac response to diving and its relationship with resting HRV appears to be gender dependent.