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Role Of Diffetent Inhibition Of RAAS In Cardiovascular Remodeling And Plasma Adrenomedullin Changing In Hypertensive Rats

Posted on:2005-06-02Degree:MasterType:Thesis
Country:ChinaCandidate:Y XingFull Text:PDF
GTID:2144360125958398Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective: Hypertension is a general disease that resulted from polygenic inheritance,environment and multiple risk factors.The important pathological significance lies in target organ damage such as heart,brain and kidney.With the improvement of hypertensive pathogenesis and the rapid development of hypotensor ,the aim of controlling hypertension has been gained ,but target organ damage such as heart,brain and kidney,which lead to increasing morbidity rate,disablement rate and fatality rate are uncontrolled well,their absolute and relative incidence rate have a improving tendency.The common pathological mechanism of target organ damage—cardiovascular remodeling played a vital role,which has become a popular topic.Experimental and clinical data showed that renin-angiotensin-aldosterone system(RAAS) increased cardiovascular remodeling,including hypertrophy and proliferation of vascular smooth muscle cell(VSMC), fibrosis and changing of neurohormonal activation.Adrenomedullin(ADM),a novel cardiovascular–active peptide,was reported to play a role in hypotension,vasadilation ,inhibition of angiotensin Ⅱ and aldosterone,and attenuate progression of left ventricular dysfunction which resulted in improvement of survival.Both Perindopril and Spironolactone that inhibit RAAS in different part have been reported to attenuate the thickness of heart and aorta,frbrosis and to improve cardiovascular remodeling and function.The investigation is on the base of the method of abdominal aortic constriction,and to investigate the structural and functional changing of cardiovascular remodeling and the level of plasma ADM in hypertensive rats,and after orally take angiotensin-coverting-enzyme (ACE) inhibition Perindopril and aldosterone receptor antagonist Spironolactone,the preventive effects on cardiovascular remodeling and the level of plasma ADM are examined,and the potential role of ADM in cardiovascular remodeling is investigated,which can present theoretical basis for clinical treatment.Methods:The model of hypertensive rat was established by using the method of abdominal aortic constriction. 42 male Wistar rats were randomly divided into 4 Groups:group model(hypertensive rats serving as controls),group peri(hypertensive rats subjected to Perindopril treatment ,2mg.kg-1.d-1),group spi(hypertensive rats receiving Spironolactone treatment,20mg.kg-1.d-1),group sham(sham operated rats serving as controls).Treatment lasted for 12 weeks.After 8 weeks, animals were anesthesiaed by intraperitaneal injection of Urethane (1.2g/kg), altrosonography was used to detect the cardiac structure and function, and connected Ⅱ lead eletrocardiogram(ECG) to examine heart rate (HR), the diameter of diastolic and sistolic aorta at the top of ECG R wave and the end of ECG T wave respectively,and the thickness of aorta.All measures were repeated three times during each cardiac cycle by the same person and then calculated means. At the end of 12 weeks treatment , after anesthesiaed animals and weighed body weight(BW),systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by the method of carotid canula.Then 2 ml blood was extracted and preserved in –20℃ refrigirator .The plasma ADM were tested by radioimmuniassay (RI) in groups.And then thoracic aorta was sepatated connective tissue,and cut into vascular ring approximatedly 2mm long to evaluate the maximal dilatory responses to cumulative doses of sodium nitroprusside (SNP;10-9to 10-6 mol/l). The thickness of media ,the diameter of lumen,the diameter of aorta,and the media and lumen arca of aorta were measured,and then calculated the ratio of media thickness to diameter of lumen of aorta and the ratio of media arca to lumen arca by morphometry. The heart was excised rapidly and the left ventricle was weighed and then calculated to the ratio of heart weight to body weight (HW/BW),the ratio of left ventriclar weight to body weight(LW/BW).Results:1 The results of altrosonography: As compared with group sham,group model rats increased IVSTd,LVPWTd?...
Keywords/Search Tags:Hypertension, Cardiovascular remodeling, Spironolactone, Perindopril, Adrenomedullin
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