Effect Of Fosinopril On Expression Of Adiponectin And Its Receptor Type1in Spontaneously Hypertensive Rats

ObjectTo observe the change of the adiponectin（APN）level and insulin resistance（IR）degree in spontaneously hypertensive rats（SHR）， and understand therelationship between cardiovascular remodeling and APN. To observe theexpression of Adiponectin receptor1（AdipoR1）in musculus cardiacus andthoracic aorta, and to explicit the protective effect of AdipoR1. To discussthe influence of Fosinopril on APN, Angiotensin Ⅱ（AngⅡ）, bradykinin（BK）,insulin resistance（HOME-IR）and the expression of AdipoR1,and to discuss thepossible influencing mechanism.Methods814-week-old WKY rats were for the WKY group,and2614-week-old SHR wererandomly divided into SHR group, Fos10group and Fos20group. The Fos10groupand Fos20group were gavaged through using Fosinopril of10mg/kg.d and20mg/kg.d,the other groups were given distilled water. Measure their weight every weekand blood pressure each two weeks. After8weeks,collect blood and measure APN,AngⅡ,BK, fasting blood-glucose and fasting insulin, and calculate insulinresistance index（HOME-IR）. Calculate heart weight index (HWI) and leftventricular mass index (LVWI).Observe the cardiac and vascular morphologythrough HE dyeing, and measure media thickness (MT),luminal diameter(LD),andratio of media to lumen(MT/LD). Adopt fluorescence quantitative PCR and Western-Blot methods to measure the distribution and expression of AdipoR1.Compare each index difference in four groups of rats, analysis the factor ofaffect blood pressure and cardiovascular remodeling before and afterfosinopril.Results1. Before the experiment, the SBP levels of SHR are higher than WKY rats.During the trial period, there was no significant change on SBP in WKY group,while SBP in SHR group was gradually increased until20weeks of age. From thefirst2weeks, the SBP in both Fos10and Fos20were decreased, and remained stablefrom the sixed week. Moreover, the SBP in Fos20descend more sharply than Fos10.2. Compared with WKY, the level of APN and BK in SHR is lower, but the levelof FINS,HOME-IR and AngⅡare higher. After intervention, compared with SHR, thelevel of APN and BK in Fos10and Fos20groups are higher, but the level ofFINS,HOME-IR and AngⅡ are lower. And the result of Fos20is more notable thanFos10.3. Compared with WKY, the level of HWI and LVWI in SHR are higher, MT arethicker, and MT/LD is higher. But the level of HWI、LVWI、MT、MT/LD in Fos10and Fos20are lower than SHR group. The result of Fos20group is more notablethan Fos10.4. Cardiac muscle and thoracic aorta morphological observation showing,compared with WKY group, the volume of myocardial cell in SHR were increasedand disarranged, and interstitial fibroblasts were proliferated. the vascularsmooth muscle layer of SHR ranks in a mass and its tunica media is thicker.Compared with SHR group, the form of myocardial cell and thoracic aorta wereimproved. And the effects in Fos20group were more significant. 5. Fluorescence quantitative PCR and Western Bolt showing, compared withWKY, AdipoR1of myocardium and aorta in SHR decreased significantly. But theAdipoR1in Fos10and Fos20groups increased more sharply than SHR group. Andthe effects in Fos20group were more significant.6. Multiple stepwise regression analysis to the indicators between WKY andSHR groups showing, APN,AdipoR1,HOME-IR and AngⅡ are the impact of importantfactors for SBP. There are negative correlation between SBP and APN,AdipoR1.There are positive correlation between SBP and HOME-IR, AngⅡ. APN,AdipoR1, HOME-IR and SBP are the impact of important factors for LVWI and MT/LD.There are negative correlation between LVWI with MT/LD and APN, AdipoR1. whilethere are positive correlation between LVWI with MT/LD and HOME-IR, SBP.7. Multiple stepwise regression analysis to the indicators among SHR,Fos10and Fos20groups showing，APN,AdipoR1,HOME-IR and AngⅡare the impact ofimportant factors for SBP. There are negative correlation between SBP andAPN,AdipoR1,BK.while there are positive correlation between SBP and HOME-IR,AngⅡ. APN, AdipoR1, HOME-IR, SBP, AngⅡand BK are the impact of importantfactors for LVWI and MT/LD. There are negative correlation between LVWI withMT/LD and APN, AdipoR1, BK. while there are positive correlation between LVWIwith MT/LD and HOME-IR, SBP, AngⅡ.Conclusion1. The SBP of SHR is increasing with the age and up to20weeks of age, ittends to be stable. There is obvious cardiovascular remodeling. SHR is the idealanimal model of essential hypertension.2. There is hypoapnemia in SHR and the index will reduce with the expressionof myocardium and aorta AdipoR1. 3. It may promote to occur hypertension and cardiovascular remodeling withlower APN level, lower expression of AdipoR1and IR in SHR.4. Fosinopril can control blood pressure level and restrain cardiovascularremodeling by the mean of reducing AngⅡ,lifting BK, improving IR, lifting APNlevel and AdipoR1expression.5. The effect of Fosinopril20mg is stronger than the10mg in the progressof rising APN, lifting AdipoR1.