Effect of angiotensin II type 1 receptor blocker on osteoporotic rat femurs

Dönmez, Barış Özgür; Özdemir, Semir; Sarıkanat, Mehmet; Yaraş, Nazmi; Koç, Pınar; Demır, Necdet; Karayalçın, Binnur; Oğuz, Nurettin

doi:10.1016/s1734-1140(12)70882-4

Cited by 50 publications

(37 citation statements)

References 41 publications

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“…The study of the potential effects of Ang II and its inhibitors on bone mineral density (BMD) has been an area of intense interest and has has yielded conflicting results. While Losartan increased bone mass and strength in ovariectomized osteoporotic female rat femurs [12], it failed to improve bone mass loss in orchiectomized male rats [21]. Broulík et al found that the use of Losartan and Enalapril was not associated with increased bone mass in intact female rats [22].…”

Section: Discussionmentioning

confidence: 99%

“…Th ey also showed the expression of RAS components for the first time during fracture healing, and that ACEIs decreased fi brosis in the early phase of a fracture. Based on these findings, we have designed a study to compare the influences of ACEIs and ARBs on fracture healing and hypothesized that, owing to the substantial data that AngII exerts its effects on bone mainly via AT1 receptor [6,7,10,11,12], ARBs should be as successful as ACEIs for stimulating fracture healing.…”

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confidence: 99%

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The Effects of the Angiotensin Converting Enzyme Inhibitor Enalapril and the Angiotensin II Type 1 Receptor Blocker Losartan on Fracture Healing in Rats

Bayar¹,

Turan²,

Gülle³

et al. 2015

CIM

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Purpose: Angiotensin converting enzyme inhibitors (ACEI) and type I angiotensin receptor blockers (ARB) have been shown to exert significant effects on bone tissue via a local renin-angiotensin-aldosterone system (RAS). Th e aim of our study was to delineate their influences on fracture healing process.Methods: Sixty adult male Wistar Albino rats were divided into three groups. After undergoing surgical femoral fracture and fi xation, the ACEI group received 10 mg/kg of Enalapril, the ARB group received 10 mg/kg of Losartan and the Control group did not receive any medication. Fracture healing was evaluated at second and fift h postoperative weeks by the Lane-Sandhu radiological staging system and by histological scoring system of Huoet al. ACE expression in fracture callus was studied by immunohistochemistry.Results: Both ACEI and ARB groups showed less fibrous tissue in the fracture area at the second week, but the histologic score differences were significant only between Control and ARB groups. At the fift h week, however, both radiological and histological scores for the ACEI group were significantly higher than both ARB and Control groups, while the scores for ARB and Control groups were similar. The presence of ACE expression in fracture callus was also observed. Conclusion:ACEIs had significant positive effects on fracture repair. Losartan failed to display these stimulatory effects, which suggests that local RAS in bone tissue exerts its actions via alternative receptors or pathways than the AT1 receptor.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Effects of the Angiotensin Converting Enzyme Inhibitor Enalapril and the Angiotensin II Type 1 Receptor Blocker Losartan on Fracture Healing in Rats

Bayar¹,

Turan²,

Gülle³

et al. 2015

CIM

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“…2) The experimental studies have showed the beneficial effects of ACEI and ARB on maintaining bone health of ovariectomized (OVX) rats 11,18,19) and mice, 10,20) an animal model mimicking postmenopausal osteoporosis due to the decline of circulating estrogen level. While, given renin is the rate-limiting enzyme of the RAS, whether the RAS inhibition by inhibiting renin activity could show beneficial effects on postmenopausal osteoporosis is not known.…”

Section: )mentioning

confidence: 99%

Renin Inhibition Improves Ovariectomy-Induced Osteoporosis of Lumbar Vertebra in Mice

Zhang

Yang

et al. 2014

Biological & Pharmaceutical Bulletin

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The skeletal renin-angiotensin system (RAS) is involved in the progression of osteoporosis and the active peptide within the RAS, angiotensin II (ANG II), has deleterious effects on bones. This study was performed to investigate whether suppression of the rate-limiting step of the RAS cascade by the renin inhibitor aliskiren has a benefit on trabecular bone in osteoporotic mice. A postmenopausal osteoporosis model was induced by bilateral ovariectomy. The ovariectomized (OVX) mice were treated with a low (5 mg/kg) or high (25 mg/kg) dose of aliskiren for 6 weeks. Micro-computed tomography was performed to detect trabecular bone parameters of lumbar vertebra and to obtain 3-dimensional (3D) images. Treatment with aliskiren markedly increased bone volume over total volume (p<0.05), trabecular bone number (p<0.05), connectivity density (p<0.05), and bone mineral density (p<0.05) and reduced trabecular bone separation (p<0.05) compared to vehicle-treated OVX mice. Similarly, the 3D images were consistent with the quantitative data that showed aliskiren could markedly reverse the ovariectomy-induced pathological changes of trabecular bone. Thus, this study indicated that the treatment of estrogen-deficient mice with aliskiren could markedly increase bone mass and improve trabecular bone structure, suggesting its potential application in treating postmenopausal osteoporosis.Key words renin-angiotensin system; aliskiren; bone; osteoporosis; ovariectomy The renin-angiotensin system (RAS) is a hormonal cascade that is thought to act as a master controller of blood pressure and fluid balance within the body.1) Within classical RAS, liver secreted angiotensinogen (AGT) is enzymatically cleaved to angiotensin (ANG) I by kidney-derived renin. ANG I is, hereafter, cleaved by angiotensin-converting enzyme (ACE) to the effector hormone ANG II. It is now evident that the components of RAS, in addition to the classical pathway, are expressed and act locally in multiple tissues, 2) such as insulin secretion, 3) glomerular sclerosis, 4) renal inflammation, 5) atherosclerosis, 6) cardiac hypertrophy 7) and brain disorders. 8)Recent studies showed that the components of RAS, such as renin, ACE, and ANG II receptors, are also expressed in the local milieu of bone. 9,10) Functional studies revealed that ANG II could stimulate the differentiation and activity of osteoclasts in vivo 11) and in vitro, 12) and aggravate the loss of bone minerals in rats with osteoporosis induced by estrogen deficiency, 11) furthermore, the ANG II type 1 receptor knockout mice showed high bone mass.13) In addition, we recently demonstrated that the local RAS in bone was involved in age-related osteoporosis of aging mice, 14) bone deteriorations of mice with either obstructive nephropathy 15) or type 1 diabetes, 16) and others elucidated the involvement of skeletal RAS in the process of fracture healing in a mouse femur fracture model. 17) Therefore, the local RAS displays important biological actions in bone tissue.Currently, besides the applications in the...

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“…Typical force-displacement and stress-strain curves obtained from the tensile test were analyzed as described before (Donmez et al 2012). By this way ultimate tensile load, ultimate tensile strength, strain, stiffness, tensile modulus (Young's modulus) was measured.…”

Section: Calculation Of Biomechanical Datamentioning

confidence: 99%

“…Furthermore the tensile modulus (MPa) was then calculated as follows: E = Δσ/Δε where ε is the strain. The strain (% displacement) was obtained by the equation: ε = ΔL/L 0 , where ∆L is the change in the length and L 0 is the original length (Donmez et al 2012). …”

Section: Calculation Of Biomechanical Datamentioning

confidence: 99%

Sodium tungstate alleviates biomechanical properties of diabetic rat femur via modulation of oxidative stress

Dönmez

Ozturk²,

Sarıkanat³

et al. 2014

gpb

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Abstract. Diabetes mellitus leads to bone disorders such as osteopenia and osteoporosis that can increase fracture risk. On the other hand, sodium tungstate is an inorganic compound which exerts anti-diabetic activity in experimental studies due to its suggested insulin-mimetic or antioxidant activity. Therefore this study was designed to investigate the effect of tungstate on bone quality in diabetic rat femurs. The rats were divided into four groups: Control (C), tungstate-treated control (C+Tung), diabetes (STZ-D) and tungstate-treated diabetes (STZ-D+Tung). Diabetes mellitus was induced by single injection of streptozotocin (50 mg/kg). The treated rats received 150 mg/kg/day of sodium tungstate for 12 weeks. Sodium tungstate achieved a little (17%) but significant reduction on blood glucose levels, while it didn't recover the reduced body weights of diabetic rats. In addition, impaired bone mechanical quality was reversed, despite the unchanged mineral density. Sodium tungstate administration significantly lowered the 2-thiobarbituric acid reactive substances and restored the activity of tissue antioxidant enzymes such as glutathione peroxidase, catalase and superoxide dismutase in diabetic rats. On the other hand, glutathione levels didn't change in either case. These findings indicate that tungstate can improve the reduced mechanical quality of diabetic rat femurs due probably to reduction of reactive oxygen species and modulation of antioxidant enzymes as well as reduction in blood glucose levels.

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Effect of angiotensin II type 1 receptor blocker on osteoporotic rat femurs

Cited by 50 publications

References 41 publications

The Effects of the Angiotensin Converting Enzyme Inhibitor Enalapril and the Angiotensin II Type 1 Receptor Blocker Losartan on Fracture Healing in Rats

The Effects of the Angiotensin Converting Enzyme Inhibitor Enalapril and the Angiotensin II Type 1 Receptor Blocker Losartan on Fracture Healing in Rats

Renin Inhibition Improves Ovariectomy-Induced Osteoporosis of Lumbar Vertebra in Mice

Sodium tungstate alleviates biomechanical properties of diabetic rat femur via modulation of oxidative stress

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Effect of angiotensin II type 1 receptor blocker on osteoporotic rat femurs

Cited by 50 publications

References 41 publications

The Effects of the Angiotensin Converting Enzyme Inhibitor Enalapril and the Angiotensin II Type 1 Receptor Blocker Losartan on Fracture Healing in Rats

The Effects of the Angiotensin Converting Enzyme Inhibitor Enalapril and the Angiotensin II Type 1 Receptor Blocker Losartan on Fracture Healing in Rats

Renin Inhibition Improves Ovariectomy-Induced Osteoporosis of Lumbar Vertebra in Mice

Sodium tungstate alleviates biomechanical properties of diabetic rat femur via modulation of oxidative stress

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Product

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Sodium tungstate alleviates biomechanical properties of diabetic rat femur via modulation of oxidative stress