Telmisartan use in rats with preexisting osteoporotics bone disorders increases bone microarchitecture alterations via PPARγ
Telmisartan (TEL), an angiotensin II type I receptor blocker and PPARγ partial agonist, has been used for to treat hypertension. It is known that PPARγ activation induces bone loss. Therefore, we evaluate the effects of telmisartan on PPARγ protein expression, biomechanics, density and bone microarc...
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Published in: | Life sciences (1973) Vol. 237; p. 116890 |
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Main Authors: | , , , , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
New York
Elsevier Inc
15-11-2019
Elsevier BV |
Subjects: | |
Online Access: | Get full text |
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Summary: | Telmisartan (TEL), an angiotensin II type I receptor blocker and PPARγ partial agonist, has been used for to treat hypertension. It is known that PPARγ activation induces bone loss. Therefore, we evaluate the effects of telmisartan on PPARγ protein expression, biomechanics, density and bone microarchitecture of femurs and lumbar vertebrae in SHR ovariectomized animals, a model of hypertension in which preexisting bone impairment has been demonstrated.
SHR females (3 months old) were distributed into four groups: sham (S), sham + TEL (ST), OVX (C) and OVX + TEL (CT). TEL (5 mg/kg/day) or vehicle were administered according to the groups. After the protocol, blood pressure was measured and density, microarchitecture and biomechanics of bone were analyzed. Western blotting analysis was performed to evaluate PPARγ protein expression in the bones.
Castration induced a deleterious effect on mineral density and trabecular parameters, with telmisartan enhancing such effects. Telmisartan increased PPARγ levels, which were at their highest when the treatment was combined with castration. As to biomechanical properties, telmisartan reduced the stiffness in the castration group (CT vs. S or C group), as well as resilience and failure load in ST group (vs. all others groups).
These results demonstrated that telmisartan compromised bone density and microarchitecture in animals that shows preexisting osteoporotic bone disorders, probably via mechanisms associated with increased PPARγ. If this translates to humans, a need for greater caution in the use of telmisartan by patients that have preexisting bone problems, as in the postmenopausal period, may be in order. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0024-3205 1879-0631 |
DOI: | 10.1016/j.lfs.2019.116890 |