Remodeling Of Carotid Arteries In Spontaneously Hypertensive Rats

ObjectiveTo investigate both the characteristics of and the effects of telmisartan on the remodeling of carotid arteries in spontaneously hypertensive rats(SHR).Methods12 week-old-male SHR were randomized to 3 groups(n=10 for each),including untreated SHR group,telmisartan low dose(TelL)group and telmisartan high dose (TelH)group.Age and sex matched Wistar Kyoto rats were served as control group (WKY,n=10).Systolic blood pressure of rats(SBP)was measured before and after experimentation every 2 weeks.After 18 weeks intervention,rats were anesthetized and the carotid arteries were cut out and collected.HE,Sirius-red staining and double staining of elasticity fibrin and collagen fibrin(P/VB)were performed on the slices of carotid arteries.Media thickness(MT),lumen diameter(LD),media thickness/lumen diameter(MT/LD),media cross-sectional area(MCSA),mean nuclear area and area of collagen or elastin percentage and the ratio of elastin area/collagen area in carotid arteries media were assessed respectively with the compute-assisted image analysis system respectively.Theα-smooth muscle actin(α-SMA),fibronectin (FN)and laminin(LN)expression on the carotid arteries media were measured with immunohistochemistry staining.The apoptosis and proliferation of smooth muscle cells in carotid arteries were detected with in situ end labeling technique(TUNEL) and proliferating cell nuclear antigen(PCNA)immunohistochemistry staining respectively.The cell proliferation index(PI)and apoptosis index(AI)of carotid arteries media were calculated.Results1.After 2 weeks of intervention,the level of SBP in TelH group was significantly decreased when compared to SHR group(p＜0.01).Moreover,the effect of lowing SBP in TelH group was maintained to the end of experiment.During the experimental period,the mean of decreasing SBP was 53.26 mmHg in TelH group.However,there was not different between SHR group and TelL group(p＞0.05).2.The MY,LD,MT/LD,MCSA and the area of collagen percentage in carotid arteries media of SHR group were higher but the area of elastin percentage and the ratio of elastin area/collagen area in carotid arteries media were lower than those in WKY group respectively(p＜0.01 for each).The MT,MT/LD,MCSA and the area of collagen percentage in carotid arteries media of TelH group were lower but the area of elastin percentage and the ratio of elastin area/collagen area in carotid arteries media were higher than those in SHR group respectively(p＜0.01 for each).The MT and area of collagen percentage in carotid arteries media were reduced in TelL group but the ratio of elastin area/collagen area increased when compared with SHR group(p＜0.05 for each).3.Carotid arteries media in each group were positive withα-SMA immunohistochemistry staining,which indicated that tunica media cells were vascular smooth muscle cells(VSMCs).Mean nuclear area of VSMCs of SHR group was significantly higher than that in WKY group(p＜0.01).Mean nuclear area of VSMCs of either TelH or TelL group was significantly lower than that in SHR group respectively.(p＜0.05 for each).4.PI was not obviously difference in each group(p＞0.05).AI in SHR group was lower than that in WKY group(p＜0.01).However,AI in TelH,TelL group was higher than that in SHR group respectively(p＜0.01).PI/AI in SHR group was higher than that in WKY group(p＜0.01).Moveover,PI/AI in TelH,TelL group was lower than that in SHR group.(p＜0.01).5.The integrated optical density(IOD)of both FN and LN in the carotid arteries media in SHR group was markedly higher than that in WKY group respectively(p＜0.01).Furthermore,the IOD of FN and LN in the carotid arteries media in TelH and TelL group was markedly lower than those of SHR group respectively(p＜0.05).6.AI in carotid arterial media was significantly negative correlated with medial crosssectional area(MSCA)(r=-0.871,p＜0.01).The IOD of both FN and LN in the carotid arteries media was positively correlated respectively with the MSCA of carotid arteries(r=0.954,0.859,p＜0.01 for each).Conclusions 1.The apparent remodeling of carotid arteries in SHR(30 week-old-male)was observed.Both wall thickness and cross-sectional area of media increasing were the feature of the remodeling in media of carotid arteries.2.Both hypertrophia and proliferation-apoptosis unbalance of VSMCs may play an important role in the pathogenesis of carotid arteries remodeling in SHR.3.ECM such as collagen,FN and LN increased but elastic fibers decreased markedly in the arterial media in SHR,which suggested that ECM was also undergoing remodeling.4.Telmisartan could attenuate remodeling through its decreasing SBP,downregulation of collgen,FN,LN and VSMCs hypertrophia,but upregulation of elastin and VSMCs apoptosis on carotid arteries of SHR.