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
Main Authors: Birocale, Antonio Marcos, Ferreira de Melo, Antonio, Peixoto, Pollyana, Costalonga Oliveira, Phablo Wendell, Gonçalves Ruffoni, Leandro Dias, Takayama, Liliam Masako, Nogueira, Breno Valentim, Nonaka, Keico Okino, Rodrigues Pereira, Rosa Maria, Martins de Oliveira, José, Bissoli, Nazaré Souza
Format: Journal Article
Language:English
Published: New York Elsevier Inc 15-11-2019
Elsevier BV
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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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ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2019.116890