title: Impairing effects of angiotensin-converting enzyme inhibitor Captopril on bone of normal mice.
abstract: There are contradicting results about the effects of angiotensin-converting enzyme inhibitors (ACEIs) on bones. This study was aimed to investigate the effect of ACEI, Captopril, on bone metabolism and histology as well as the action of Captopril on skeletal renin-angiotensin system (RAS) and bradykinin receptor pathway in normal male mice. The urine, serum, tibias and femurs from normal control mice and Captopril-treated (10mg/kg) mice were collected for biochemical, histological and molecular analyses after drug administration for eight weeks. The mice after the treatment with Captopril had a significant decrease of serum testosterone level. The histological measurements showed the loss of trabecular bone mass and trabecular bone number, and the breakage of trabecular bone network as well as the changes of chondrocyte zone at epiphyseal plate in Captopril-treated mice. The defect of Captopril on trabecular bone was reflected by the quantitative bio-parameters from micro-CT. The expression of renin receptor and bradykinin B2 receptor (B2R) was significantly up-regulated in tibia of mice upon to the Captopril treatment, which decreased the ratio of OPG/RANKL and the expression of osteoblastic factor RUNX2. Furthermore, Captopril treatment resulted in the increase of pAkt/Akt and pNFκB expression in tibia. The present study revealed the impairing effects of Captopril on bone via interfering with the circulating sex hormone level and B2R pathway, which suggests that the bone metabolism of patients need to be carefully monitored when being prescribed for ACEIs.
authors.affiliation: School of Pharmacy, Nantong University, Nantong 226001, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Nantong University, Nantong 226001, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xia
authors.affiliation: School of Pharmacy, Nantong University, Nantong 226001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.affiliation: School of Pharmacy, Nantong University, Nantong 226001, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
authors.forename: Man-Sau
authors.initials: MS
authors.lastname: Wong
authors.affiliation: School of Pharmacy, Nantong University, Nantong 226001, China. Electronic address: riceandtiger@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001847:Bone Diseases / Q000139:chemically induced*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002216:Captopril / Q000633:toxicity*; D011905:Genes, ras / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D006180:Proton-Translocating ATPases / Q000187:drug effects / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D013977:Tibia / Q000187:drug effects / Q000378:metabolism; D000093342:Prorenin Receptor
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D006180:Proton-Translocating ATPases; D043782:Receptor, Bradykinin B2; D011956:Receptors, Cell Surface; D013739:Testosterone; C583530:ATP6AP2 protein, mouse; D000093342:Prorenin Receptor
keywords: Angiotensin II; Angiotensin-converting enzyme inhibitor; Bone; Bradykinin receptor; Captopril; Renin–angiotensin system