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.

Conclusion: 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.