| IntroductionHeart rate variability(HRV) is the time variance of sinus beat-to-beat in a period of time.HRV reflects the tense and balance of autonomic nervous system (ANS).Besides the effects of ANS,endocrine factors,body temperature,body position and mental factors also affecting heart rate variability.The renin-angiotensin is one of the endocrine factors influencing HRV.AngiotensinⅡ(AngⅡ) is the most considerable bioactive compound of RAS,which reduces the baroreflex bradycardia response via angiotensinⅡreceptors I(AT).Baroreceptor responses are very rapid,acting within a few seconds to compensate for any sudden change in blood pressure,e.g,increasing in arterial pressure lead to reducing the heart rate via modulating the activity in sympathetic,sympathetic vasoconstrictor and parasympathetic nerves.The resetting point of the baroreflex is a reference level of the mean arterial pressure.It has been suggested that the effect of resetting of the cardiac baroreflex caused by circulating AngⅡis mediated via the AT1 receptors.Patients with essential hypertension and congestive heart failure,concentration of their plasma AngⅡare higher than healthy people,while the index of their HRV are lower than the healthy people.The study of our laboratory suggested that intravenous infusion of AngⅡcan decrease the index of HRV,but the proper mechanism of its effects are still unkown.We presume that the effects caused by intravenous infusion of AngⅡto HRV are mediated by its resetting action on the baroreflex control of HR.Therefore,the present study used anesthetized rats,microinjected the AT1 inhibitor in order to eliminate the effect of AngⅡon baroreflex and analyzed whether the changes of HRV caused by intravenous infusion of AngⅡrefer the baroreflex resetting effect.The experiment also observs the changes of HRV after AT injection. Materials and Methods1.Animals and experimentAdult male Wistar 280 g～320 g,obtained from the Experimental.Animal Center, China Medical University.Animals were caged individually and had free access to food and water.Before experiment each rat was placed individually in a plastic cage adapting the experiment,light and darkness were alternated with light 6:00 to 18:00. The ambient temperature of the animal room was(24±2)℃;and the humidity was (55±5)%.2.Experiment groups and protocol(1) control group:vena femoralis injection of 5%dextrose(3ml/kg),after 50min intravenous infusion of AngⅡ(20ng/kg/min).(n=10).(2) AT1 inhibitor group:vena femoralis injection of AT1 inhibitor losartan potassium 5mg/kg,after 50min intravenous infusion of AngⅡ(20ng/kg/min).(n=10).3.Surgical procedure,ECG and BP recording20%urethane injected celiac anesthesia,6.5 ml/kg,rats were placed in a dorsal position.Snip its clothing hair,slit cutaneous covering along courser of the blood vessel derection.Dissect anadesma and muscles bluntly in order to reveal the femoral vein and artery,which will be liberated with clew under them respectively.Then the distal end of the blood vessel is ligatid while the proximal end is clipped by a bulldog clamp.And then cut the femoral artery with eye scissors near to the clew,after which a arterial cannula can be insert into the arterial.Finally,fix the arterial cannula with a clew.To insert a venous cannula is the same.All animals were collected uninterrupted ECG from anesthesia state to all medicines ending according toⅡjoin.Powerlab4/25 biology signal collecting system shoud be calibrated before measure blood pressure.The arterial cannula of femoral artery was connected to a pressure transducer together with which were switch into the Powerlab4/25 system.The signal and data of ECG and BP were collected and saved in the computer.The experiment was undertake at 8:00～12:00.4.Baroreflex function tests The baroreflex function were tested 30min after the operation,20min after dextrose or AT1 inhibitor(losartan) injection and 10min after intravenous infusion of AngⅡ.MAP was produced by infusion of phenylephrine,and the accompanying reflex changes in HR were measured.Baroreceptor were loaded with progressive ihtravenous injection of PE(4,10,15,20μg/kg),respectively.Each dose of PE injection was separated by 2-3min.At least 20 minutes was allowed for stabilization before the next injection or infusion.5.HRV analysisSelect 5 min continuous ECG before each baroreflex function test.Analyzed all data with HRV software.6.Statistical analysisExperiment data were indicated as mean±SE.Most analyses were performed by were assessed by analysis of variance.Student't test was used for comparing two independent samples.To analyze baroreflex responses,the data were subjected to linear regression analysis.A value of P＜0.05 was considered to be statistic significance.ResultsAfter intravenous infusion AngⅡin control group,MAP increased significantly (P＜0.05) compared with the basic value after surgery.HR were not significant (P>0.05);During the infusion,LFn and LF/HF of frequency domain were increased (P＜0.05),HFn of frequency domain was decreased(P＜0.05).Among AngⅡinfusion, the MAP-HR baroreflex curve moved to right upper,but resetting points of the barorecptor reflex were not significantly increased(P=0.058);the slopes of the MAP-HR barroreflex curve were not changed either(P＞0.05).After intravenous injection of losartan,compared with the basic value after the surgery,MAP was not significant(P＞0.05),HR increased gradually,its changes were not significant.Losartan has no effect on parameters of HRV and the baroreflex response.Compared with the control group,after losartan injection followed by intravenous infusion of AngⅡ,MAP,LFn and LF/HF were decreased significantly(P＜0.01),HFn increased(P＜0.01).The MAP-HR baroreflex curve not moved,the change of resetting points of the baroreceptor reflex was decreased significantly(-5.62±6.04 vs11.5±5.12, (P＜0.05).The change of slopes of the baroreceptor reflex was not significant (P＞0.05).Conclusion(1) Intravenous infusion of AngⅡcaused resetting of the baroreceptor reflex;the parameters of HRV which reflex the tone of parasympathetic de creased notably.After blocked the AT1 receptor,the effects of AngⅡon HRV and baroreflex were dispeared.These mean that AngⅡacts on AT1 receptor influencing HRV,and the mechanisms of this may contain the resetting effect on the baroreceptor response of AngⅡ.(2) After injection of losartan,there were no changes in MAP,baroreceptor reflex resetting point,the MAP-HR curve,HR and HRV parameters,which means acute injection of AT1 receptor antangonist has no influence on HRV and the baroreflex.
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