title: Effect of angiotensin II type I receptor blocker losartan on bone deterioration in orchiectomized male hypertensive and normotensive rats.
abstract: 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 losartan (10 mg×kg(-1)×d(-1)); and Group 4, ORX+high-dose losartan (25 mg×kg(-1)×d(-1)). Blood pressure was recorded weekly. SHAM and ORX operations were performed, followed by daily losartan 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 losartan significantly increased DPD in urine in both SHR and WKY. Apart from marginal favorable changes in bone architecture in WKY treated with high-dose losartan, losartan did not show significant effect on BMD, bone area, bone microarchitecture, and mechanical properties in both SHR and WKY.
  
  
  CONCLUSIONS
  Angiotensin II type I receptor blocker losartan was not able to demonstrate significant effect on ORX-induced bone deterioration in both hypertensive and normotensive rats.
authors.affiliation: Department of Orthopaedics, The Affiliated Hospital to Nantong University, Nantong, Jiangsu, China.
authors.forename: Ya-feng
authors.initials: YF
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.forename: Timothy C Y
authors.initials: TC
authors.lastname: Kwok
authors.forename: Benson H Y
authors.initials: BH
authors.lastname: Yeung
authors.forename: Guo-dong
authors.initials: GD
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D009919:Orchiectomy; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013599:Systole / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan