Remodeling of intrarenal small arteries in rats with diabetic hypertension and influence of telmisartan on ;the remodeling

HUANG Xin-tao; HONG Hua-shan; LI Xiao-hong; LI Hong-yan; YAN Xiao-jing; LI Zhi-heng; LI Zhong-yuan

doi:10.3969/j.issn.1674-4055.2015.06.31

Abstract：Objective To investigate the remodeling of intrarenal small arteries (IRSAs) in diabetic spontaneous hypertension rats (DSHR), and the influence of telmisartan on IRSAs remodeling. Methods Male SHR rats (12 weeks old, n=40) were randomly divided into SHR group, DSHR group, high-dose group and low-dose group (each n=10), and at the same time, WKY rats (12 weeks old, n=20) were randomly divided into normal control group (WKY group) and diabetic WKY group (DWKY group, each n=10). The low-dose group and high-dose group were intragastrically given telmisartan, and other groups were intragastrically given distilled water after model establishment with STZ. IRSAs were divided, according to external diameters of vessels, into 20μm-49μm group (20-49 group), 50μm-99μm group (50-99 group) and 100μm-200μm group (100-200 group). The wall area (WA), wall thickness (WT) and internal diameter (ID) of IRSAs and ratio of WT to ID (WT/ID) were calculated by using computer-assisted image analysis system in all groups. IRSAs sections were stained withα-SMA, ED1 and COLIII immunohistochemistry technique for counting ED1 positive cells and comparing integrated optical density (IOD) of COLIII in all groups. The wall cell apoptosis of IRSAs was detected by using TUNEL, wall cell proliferating of IRSAs was reviewed by using PCNA immunohistochemistry technique, and apoptosis index (AI) and proliferating index (PI) were calculated respectively. Results ①Compared with WKY group, WT increased, ID decreased significantly (all P<0.05). IRSAs remodeling was similar in 50-99 group and 100-200 group, but increased more significantly in 50-99 group. Compared with DWKY group and SHR group, WT, WA and WT/ID increased (all P<0.05) in DSHR group. After telmisartan intervention for 8 w, WT, WT/ID and WA were improved significantly in high-dose group and low-dose group compared with DSHR group (all P<0.05). ②The positive rate of PCNA increased in SHR group and DWKY group compared with WKY group. PI decreased significantly in high-dose group and low-dose group compared with DSHR group (P<0.01). PCNA positive was more significant in SHR than that in rats with only diabetes or hypertension. Telmisartan in high-dose or low-dose decreased significantly PCNA positive cells after 8 w, but high-dose telmisartan had more significant effect. ③Compared with WKY group, AI decreased in DSHR group, SHR group and DWKY group (all P<0.01). ④Compared with WKY group, the number of glomeruli decreased significantly in DWKY group [(423.8±37.4) vs. (338.7±40.5), all P<0.01], and there was no glomeruli decrease in SHR group. Compared with DWKY group, the number of glomeruli decreased in DSHR group [(301.4±35.2) vs. (338.7±40.5), P<0.05]. ⑤Compared with WKY group, IOD of COLⅢincreased in SHR group and DWKY group (all P<0.05). Compared with SHR group and DWKY group, IOD of COLⅢincreased in DSHR group (all P<0.05). IOD of COLⅢdecreased in high-dose group compared with DSHR group (P<0.01). ⑥High-dose telmisartan reduced blood pressure, and low-dose telmisartan had no effect on blood pressure. The increases of WT, WA and WT/ID were relieved, proliferation was reduced, decrease of glomeruli number was alleviated and COLⅢoverdeposition was decreased in treatment groups, which was more significant in high-dose group. Conclusion ①The remodeling of IRSAs occurred in DWKY group, SHR group and DSHR group, and was more significant in DSHR group. ②The remodeling of RSAs is mainly related to the proliferation of VSMC, abnormal apoptosis and COLⅢoverdeposition. ③High-dose telmisartan and low-dose telmisartan all can alleviate the remodeling of RSAs, and high-dose telmisartan is more effective. The relieving effect of telmisartan on vascular remodeling maybe related to the improvement of proliferation and apoptosis balance.