Effect Of The LCLAs On Expression Of ET And Vascular Remodeling In Renal Hypertensive Rats

Objective:1.To investigate the effects of the Lobelia Chinensis Lour Alkaloids(LCLA) on ET-1mRNA expression and endothelin(ET) synthesis and release in renal hypertensive rats (RHRs).2.To investigate the effect and mechanism of Lobelia Chinensis Lour Alkaloids(LCLAs) on vascular remodeling in renal hypertensionMethods:The Glodblatt renovascular hypertension model was induced in rats by two-kidney one clip method. After 4 weeks the rats were divided into 3 groups, including the hypertensive group, the captopril group and the LCLA group, while the control group was given sham - operation. Treatment lasted for 8weeks.Blood pressure was detected in 1^th,4^th and 8^th week after treatment.After 8 weeks,using in situ hybridization to observe ET-1 mRNA expression in peripheral blood leucocytes. Using immunohistochemical technique to count positive rate of ET in"en face"preparations of arterial endothelium to reflect the synthesis of ET. Using radioimmunoassay to examine the level of ET in serum and the plasma renin activity (PRA) .The parameters of vascular remodeling ,including media thickness(MT) , luminal internal diameter (LD) , ratio of MT/LD and ratio of media cross-sectional area to lumen area(MCSA / LA) were measured through the Weigert staining photos of the abdominal aorta and the renal artery . Using Masson staining to measure the expression of collagen in abdominal aorta and the renal artery . Using Masson staining to measure interstitial collagen volume fraction (CVF) and perivascular collagen area(PVCA) in heart. Expression of collagen I was measured by immunohistochemistry method. The heart was excised rapidly and the left ventricle was weighed and then calculated to the ratio of left ventriclar weight to body weight(LWBW).Results:Before treatment,the blood pressure of the hypertensive group was higher than the sham - operation group.After 8 weeks, the blood pressure of the hypertensive group was raised,which was higher than the other three groups (p<0.05). The blood pressure of the LCLA group wasnot decreased,but it was lower than the hypertensive group s(p<0.05). The blood pressure of the captopril group was decreaced ,which was lower than the hypertensive group(p<0.05) and the LCLA group s(p<0.05) . The plasma concentration of ET, positive rate of ET in arterial endothelium, and positive rate of ET-1mRNA in peripheral blood leucocytes were increased significantly in hypertensive rats. After treated with LCLA for 8w, ET-1mRNA expression and ET synthesis and release was inhibited(P<0.05). The PRA was significantly increased in hypertensive rats compared with sham rats(P<0. 05), which was reduced in LCLAs group when compared to control group. In captopril group, no inhibitory effect on PRA was observed when compared with control group or LCLAs group(p>0.05). The MT, the ratio of MT/LD,MCSA/LA and the expression of collagen on abdominal aorta were significantly increased in hypertensive rats compared with sham rats(P<0. 05). After treatment with LCLAs or captopril ,the MT, the ratio of MT/LD, MCSA/LA and the expression of collagen on abdominal aorta were significantly decreased (P<0. 05). The interstitial collagen volume fraction (CVF) and perivascular collagen area(PVCA) in heart and the ratio of left ventriclar weight to body weight(LWBW) were significantly increased in hypertensive rats compared with sham rats(P<0. 05). After treatment with LCLAs ,the CVF , the PVCA and the LWBW were deceased in LCLAs group, but it doesnot have the statistical significance(P>0. 05); the CVF , the PVCA and the LWBW of captopril group were lowered than the hypertensive group(P<0. 05). Conclusions:1.The expression of ET was increased in RHRs. The LCLA can inhibit the expression of ET in the transcriptional and translational level which may be effective to the preventing and treatment of the renal hypertension.2.The vascular remodeling occurs in renal hypertensive rats. LCLA can inhibit the synthesis of the collagen and reduce PRA, which may reverse the vascular remodeling in hypertensive rats.