Effect of angiotensin II type I receptor blocker losartan on bone deterioration in orchiectomized male hypertensive and normotensive rats  

作　　者：ZHANG Ya-feng QIN Ling Timothy CY Kwok Benson HY Yeung LI Guo-dong LIU Fan 

机构地区：[1]Department of Orthopaedics, The Affiliated Hospital to Nantong University, Nantong, Jiangsu 226001, China [2]Department of Medicine and Therapeutics , Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China [3]Department of Orthopaedics and Traumatology , Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China

出　　处：《Chinese Medical Journal》2013年第14期2661-2665,共5页中华医学杂志（英文版）

基　　金：This study was partially supported by a direct research grant from The Chinese University of Hong Kong （No. 2006.2.017）, the Natural Science Foundation of Jiangsu Province, China （No. BK2010285）, and the Collegiate Natural Science Fund of Jiangsu Province, China （No. 10KJB320015）.

摘　　要：Background Epidemiological study showed that the use of angiotensin-converting enzyme inhibitors was associated with higher bone mineral density （BMD） in older people, especially male subjects, which suggested that angiotensin II may have a detrimental effect on bone. Therefore, blocking its effect may have a beneficial effect on bone health. Methods Six-month-old male spontaneously hypertensive rats （SHR） and normotensive Wistar Kyoto rats （WKY） were used. Animals of each model were randomly assigned to the following four groups： Group 1, SHAM operated＋vehicle; Group 2, orchidectomy （ORX）＋vehicle; Group 3, ORX＋low-dose Iosartan （10 mg.kgl.dl）; and Group 4, ORX＋high-dose Iosartan （25 mg-kg-l.d-1）. Blood pressure was recorded weekly. SHAM and ORX operations were performed, followed by daily Iosartan and vehicle treatment from day 4 after operation for 16 weeks. Serum and 24-hour urine samples were collected for measurement of bone turnover markers before euthanasia and then the left femur was collected for measurements of BMD and microarchitecture before mechanical test. Results Urine deoxypyridinoline/urine creatinine （DPD/Cr） ratio was significantly higher in SHR than in WKY. BMD and microarchitecture parameters also showed bone deterioration in SHR. After ORX, serum osteocalcin concentration decreased and urine DPD/Cr ratio increased significantly accompanied by a significant decrease in cortical and trabecular BMD and cortical bone thickness in both WKY and SHR. High-dose Iosartan significantly increased DPD in urine in both SHR and WKY. Apart from marginal favorable changes in bone architecture in WKY treated with high-dose Iosartan, Iosartan did not show significant effect on BMD, bone area, bone microarchitecture, and mechanical properties in both SHR and WKY. Conclusion Angiotensin II type I receptor blocker Iosartan was not able to demonstrate significant effect on ORX-induced bone deterioration in both hypertensive and normotensive rats.Background Epidemiological study showed that the use of angiotensin-converting enzyme inhibitors was associated with higher bone mineral density （BMD） in older people, especially male subjects, which suggested that angiotensin II may have a detrimental effect on bone. Therefore, blocking its effect may have a beneficial effect on bone health. Methods Six-month-old male spontaneously hypertensive rats （SHR） and normotensive Wistar Kyoto rats （WKY） were used. Animals of each model were randomly assigned to the following four groups： Group 1, SHAM operated＋vehicle; Group 2, orchidectomy （ORX）＋vehicle; Group 3, ORX＋low-dose Iosartan （10 mg.kgl.dl）; and Group 4, ORX＋high-dose Iosartan （25 mg-kg-l.d-1）. Blood pressure was recorded weekly. SHAM and ORX operations were performed, followed by daily Iosartan and vehicle treatment from day 4 after operation for 16 weeks. Serum and 24-hour urine samples were collected for measurement of bone turnover markers before euthanasia and then the left femur was collected for measurements of BMD and microarchitecture before mechanical test. Results Urine deoxypyridinoline/urine creatinine （DPD/Cr） ratio was significantly higher in SHR than in WKY. BMD and microarchitecture parameters also showed bone deterioration in SHR. After ORX, serum osteocalcin concentration decreased and urine DPD/Cr ratio increased significantly accompanied by a significant decrease in cortical and trabecular BMD and cortical bone thickness in both WKY and SHR. High-dose Iosartan significantly increased DPD in urine in both SHR and WKY. Apart from marginal favorable changes in bone architecture in WKY treated with high-dose Iosartan, Iosartan did not show significant effect on BMD, bone area, bone microarchitecture, and mechanical properties in both SHR and WKY. Conclusion Angiotensin II type I receptor blocker Iosartan was not able to demonstrate significant effect on ORX-induced bone deterioration in both hypertensive and normotensive rats.

关 键 词：ANGIOTENSIN angiotensin II type I receptor blocker osteoporosis ORCHIDECTOMY rat 

分 类 号：R544.1[医药卫生—心血管疾病]