Effects Of Chronic Intermittent Hypobaric Hypoxia On Heart Rate Variability In Obese Zucker Rats

It is well known that obese individuals have a high prevalence of cardiovascular disease(CVD),and autonomic nervous dysfunction will increase CVD risk.Obese people or animals are often in an unbalanced state due to imbalanced autonomic regulation of the heart,and the decreased activity of the vagus nerve and the increased activity of the sympathetic nerve,which may result in dysfunction and disease in cardiovascular,metabolic and endocrine systems.Obese Zucker rats are homozygous individuals(fa/fa)of the fa gene deficiency,which are leptin receptor mutation,mainly manifested as abdominal obesity,hyperinsulinemia,impaired glucose tolerance,hyperleptinmia and high blood pressure.Continuous changes in cardiac cycle performance in the RR interval are generally described as heart rate variability(HRV).The heart rate changes depend on the sympathetic and parasympathetic balance in different time or state of heart rate cycle and usually reflect the regulation of autonomic nervous system on heart rate in sinus node level.So HRV can be used to evaluate the health status of the heart and autonomic nerve regulation.In recent years,the beneficial effects of chronic intermittent hypobaric hypoxia(CIHH)has been widely recognized and concerned.Our previous study demonstrated that CIHH treatment has cardiac protection,promoting recovery of cardiac function,limiting infarct area and antagonizing arrhythmia induced by ischemia/reperfusion.Multiple mechanisms are involved in the protective effect of CIHH,such as augmentation of cardiac antioxygenation,induction of heat shock proteins,inhibition of apoptosis,activation of ATP-sensitive K+ channels,and inhibition of mitochondrial permeability transition pores.In renal vascular hypertension rats,CIHH showed an anti-hypertensive effect through facilitation of arterial baroreflex and enhancement of vessel dilation.In diabetes rats,CIHH showed a protective effect against diabetes and diabetic nephropathy through anti-inflammation and improvement of insulin resistance.In fructose induced metabolic syndrome rats,CIHH can ameliorate nonalcoholic fatty liver disease.In addition,CIHH has been proved to have improvement in collagen-induced arthritis,immune regulation,glycolipid metabolism,and so on.But whether CIHH has effect in autonomic regulation in obese rats is not clear and the effect of CIHH on HRV in obese rats has not been reported.Objective:The aim of this study was to investigate the change of HRV in obese Zucker rats and the effect of CIHH on HRV in obese Zucker rats by using biotelemetry technique and frequency domain analysis,so as to identify effect of CIHH on cardiac autonomic nerve regulation.Methods:Male Lean Zucker rats and Obese Zucker rats were used in this study.Age-matched rats were divided into three groups: obese Zucker rats(OZRs),lean Zucker rats(LZRs)and lean to obese Zucker rats feeding with high fat diet(L-OZRs).Under anesthesia rats got an abdominal operation and the implanted sensors were imbedded.Physiological signals of arterial blood pressure and cardiac electricity from conscious rats were transmitted wirelessly and received by external signal receiving devices.After 4-week recovery from operation,rats were put into a hypobaric chamber to get a hypobaric hypoxia treatment simulating 5,000-m altitude(PB = 404 mmHg,Po2 = 84 mmHg),6 h daily,for 28 days.Heart rate from electro-signals was automatically analyzed with Powerlab Chart7 and Dataquest ART System2.0 programs.Spectrum analysis parameters were obtained including low frequence(LF),high frequence(HF),and LF/HF.Besides,rats were treated with a 10-min acute normobaric hypoxia(10% of oxygen)before and after CIHH treatment respectively.At end of experiment,blood samples were acquired from inferior vena cava of rats and serum leptin level were measured by using an enzyme-linked immunosorbent assay kit.Results:1 Baseline body weight was higher in OZRs and L-OZRs rats than that in LZRs rats.CIHH treatment had no effect on body weight in LZRs rats(P>0.05),but significantly decreased body weight in OZRs and L-OZRs rats(P <0.05).2 Baseline arterial blood pressure was higher in OZRs and L-OZRs rats than that in LZRs rats(P<0.05).CIHH treatment had no effect on arterial blood pressure in LZRs rats(P>0.05),but significantly decreased arterial blood pressure in OZRs and L-OZRs rats(P <0.05).3 Baseline heart rate was lower in OZRs rats than that in LZRs rats(P<0.05).CIHH treatment decreased heart rate in all rats(P <0.05).4 Before CIHH treatment,normalized baseline LF(nLF)was decreased,and nomalized baseline HF(nHF)was increased,and LF/HF was decreased in OZRs rats compared with OZRs and L-OZRs rats.CIHH treatment increased nLF and decreased LF/HF in OZRs rats significantly(P<0.05).5 Before CIHH treatment,acute normobaric hypoxia increased blood pressure and heart rate in the same range for all rats(P>0.05),but the increase was bigger in OZRs and L-OZRs rats than LZRs rats(P<0.05).After CIHH treatment,the increase of blood pressure by acute normobaric hypoxia was bigger in OZRs rats than LZRs and L-OZRs rats(P<0.05),and the increase of heart rate by acute normobaric hypoxia was bigger in OZRs and L-OZRs rats than LZRs rats(P<0.05).6 Before CIHH treatment,acute normobaric hypoxia increased nLF in OZRs rats significantly(P<0.05).After CIHH treatment,acute normobaric hypoxia decreased nLF in OZRs rats significantly(P<0.05).Before CIHH treatment,acute normobaric hypoxia decreased nHF in OZRs rats significantly(P<0.05).However,there was no significant difference of nHF during acute normobaric hypoxia after CIHH treatment in OZRs in nHF(P> 0.05).7 Before CIHH treatment,baseline serum Leptin level in OZRs rats was significantly higher than that in LZRs and L-OZRs rats(P<0.01).CIHH treatment decreased serum Leptin level in OZRs rats(P<0.05),but had no effect on serum Leptin level in LZRs and L-OZRs rats(P<0.05).Conclusion:The present study investigated the effect of CIHH on cardiac autonomic nerve regulation in obese Zucker rats through using biotelemetry technique and HRV analysis method for the first time.Results demonstrated that Obese Zucker rats had significant changes in HRV,increased vagal tone,and decreased sympathetic tensions;CIHH treatment reduced the autonomic nervous function changes in Obese Zucker rats and buffered acute hypoxia on Obese Zucker rats Autonomic nerve;CIHH treatment of autonomic nerve function may be related to the leptin system.