| INTRODUCTIONArterial baroreflex(ABR) is one of the most important mechanisms regulating cardiovascular activities.Its function can be expressed as baroreflex sensitivity(BRS). Over the past 20 years,it was reported that ABR function was significantly related to the prognosis of acute cardiovascular infarction,arrhythmias,heart failure and diabetes mellitas in human.These clinical observations indicated that patients with a lower BRS exhibited a shorter survival time in these diseases.Recently,we reported that ABR function played an important role in the pathogenesis and prognosis in hypertension, atherosclerosis,aconidine-induced arrhythmia and LPS-induced shock.Moreover,the important role of ABR function on stoke was also been studied.Robinson and colleagues reported that post-stroke patients with impaired BRS values(≦5.0 ms/mm Hg) had a significantly poorer prognosis than patients without impaired BRS(＞5.0 ms/mm Hg). Recently,in our department,it was found that BRS is a very important predictor for the most important complication in hypertension:stroke.Renin-angiotensive system(RAS) consists of rennin,angiotensin and angiotensin receptor.It exists anywhere in body and plays very important role in the regulation of physiological functions and the pathogenesis of cardiovascular system.Many reports have shown that RAS played an important role in the pathogenesis and prognosis in hypertension,atherosclerosis,hypertrophy,and heart failure et al.Some studies show that BRS is impaired in patients with chronic cerebrovascualr disease and the level of AngⅡis higher.In animals,there're many angiotension receptors in Nucleus of solitary tract(NTS) in the brain.AngiotensinⅡAT1 receptor antagonist is the preference antihypertensive in clinical hypertension therapy.Losartan,as the represent of AngiotensinⅡAT1 receptor antagonist,is effective and low toxicity.According to its existence in the brain,we consider that RAS must have some relationship with stroke.If the activation of Losartan is the important role of the acute cerebral ischemia,what may be the mechanisms? Does ABR function involve in it? Therefore,the present work was designed to answer these questions.METHODSExperiment 1SHR rats age 6-month were used in this experiment.They were randomly divided into two groups(n=10 in each group).Losartan(10mg/kg/d) were given in rat chow for 2 weeks in SHR.Blood pressure(BP) was then recorded during 4 hours in conscious state. And the blood pressure,heart period and BRS were continusly recorded at conscious state.Then the rats were subjected to MCA occlusion.The infarct volume and weight of the brain were measured at 24 h after operation.Experiment 2SD rats age 6-month were used in this experiment.They were randomly divided into two groups(n=10 in control n=10 in losartan treatment group).Then AngⅡor CSF(100 nL) were injected into NTS of treated and control rats,respectively.Then the rats were subjected to MCA occlusion.The infarct volume and weight of the brain were measured at 24 h after operation.Experiment 3SD rats age 6-month were used in this experiment.They were randomly divided into two groups(n=10 in control n=10 in losartan treatment group).Then losartan or CSF(100 nL) were injected into NTS of treated and control rats,respectively.Then the rats were subjected to MCA occlusion.The infarct volume and weight of the brain were measured at 24 h after operation.Experiment 4SHR rats age 6-month were used in this experiment.They were randomly divided into two groups (n=10 in each group).The blood pressure,heart period and BRS values were measured in both 2 group rats at conscious state.Then AngⅡor CSF(100 nL) were injected into NTS of treated and control rats, respectively.And the blood pressure,heart period were continusly recorded at conscious state.BRS were determined at 4,12,24 hours after NTS injection. Experiment 5SHR rats age 6-month were used in this experiment.They were randomly divided into two groups(n=10 in each group).The blood pressure,heart period and BRS values were measured in both 2 group rats at conscious state.Then losartan or CSF(100 nL) were injected into NTS of treated and control rats,respectively.And the blood pressure,heart period were continusly recorded at conscious state.BRS were determined at 4,12,24 hours after NTS injection.RESULTSIn SHR,the BRS values were significantly increased,and the infarct size was markedly decreasd in losartan treatment group.Meanwhile,the BRS values were significantly decreased and the cerebral infarct size was larger in rats treated by AngⅡinjection into NTS.In losartan NTS injection groups,BRS values were significantly increased and the cerebral infarct size was smaller than untreated rats.CONCLUSIONBeside blood pressure reduction,the improvement of ABR function might be another important mechanism in the prevention of cerebral ischemia in rat treated by losartan. NTS might be the potential effect site.
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