title: Involvement of Renin-Angiotensin System in Damage of Angiotensin-Converting Enzyme Inhibitor Captopril on Bone of Normal Mice.
abstract: This study was performed to investigate the effect of angiotensin-converting enzyme inhibitor, captopril, on bone metabolism and histology, and the action of captopril on the components of the skeletal renin-angiotensin system (RAS) and bradykinin receptor in normal male mice. The mice were orally administered captopril (10 mg/kg) for 4 weeks with vehicle-treated mice as normal control. The histology of trabecular bone at the distal femoral end was determined by hematoxylin & eosin, Safranin O and Masson-Trichrome staining. The captopril-treated mice showed a decreased level of testosterone (p<0.05) and procollagen type I N-terminal propeptide (p<0.05) in serum as compared to those in the control group. Captopril has detrimental effects on trabecular bone as demonstrated by the loss of cancellous bone mass and network connections as well as changes to the chondrocytes zone. The expression of angiotensin-converting enzyme (p<0.05), renin receptor (p<0.01), angiotensin II (p<0.05) and bradykinin receptor 2 (p<0.05) was significantly up-regulated following the captopril treatment. Thus, the potential underlying mechanism of the damage of captopril on bone can be attributed the increased activity of local bone RAS and the activation of bradykinin receptor.
authors.affiliation: Center for Systems Biomedical Sciences, University of Shanghai for Science and Technology.
authors.forename: Jin-Xin
authors.initials: JX
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001920:Bradykinin / Q000097:blood; D002216:Captopril / Q000009:adverse effects*; D024042:Collagen Type I / Q000097:blood; D008297:Male; D008813:Mice, Inbred ICR; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010748:Phosphopeptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D018002:Receptors, Bradykinin / Q000378:metabolism*; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System; D013739:Testosterone / Q000097:blood; D015854:Up-Regulation
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D024042:Collagen Type I; C062121:N-propeptide type I collagen; D010748:Phosphopeptides; D011347:Procollagen; D018002:Receptors, Bradykinin; D000804:Angiotensin II; D013739:Testosterone; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D001920:Bradykinin