Chronic treatment with angiotensin AT1 receptor antagonists reduced serum but not bone TGF-beta1 levels in ovariectomized rats.
Approximately 50% of hypertensive patients are postmenopausal women; therefore, any antihypertensive therapy must not adversely affect bone loss in this population. Recently, however, concern has been raised that use of angiotensin AT1 receptor antagonists may increase the tendency to develop postmenopausal osteoporosis by decreasing transforming growth factor-beta1 (TGF-beta1), which has been implicated in bone mass maintenance. In the present study, we selected telmisartan and valsartan as representatives of angiotensin AT1 receptor antagonists and used ovariectomized (OVX) rats as a model of human postmenopausal osteoporosis. After 3 months treatment with telmisartan (5 mg/kg daily) or valsartan (10 mg/kg daily), OVX rats showed no signs of adverse effects on bone mineral density of the lumbar vertebrae (L1-L5) or the total femur, nor did treatment affect serum levels of osteocalcin and osteoclast-derived tartrate-resistant acid phosphatase (TRACP-5b). Bone TGF-beta1 content remained unchanged, although treatment with telmisartan and valsartan significantly reduced serum TGF-beta1 levels (p < 0.05). In conclusion, chronic treatment with angiotensin AT1 receptor antagonists reduced serum but not bone TGF-beta1 levels and did not accelerate ovariectomy-induced bone loss in rats.
Li
Yong-Qi
YQ
Department of Pharmacology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, P.R. China.
Ji
Hui
H
Shen
Yang
Y
Ding
Li-Ju
LJ
Zhuang
Pei
P
Yang
Yu-Lin
YL
Huang
Qiu-Ju
QJ
D000135:Acid Phosphatase / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000633:toxicity*; D000818:Animals; D001562:Benzimidazoles / Q000633:toxicity; D001565:Benzoates / Q000633:toxicity; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000139:chemically induced* / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071681:Tartrate-Resistant Acid Phosphatase; D000077333:Telmisartan; D013777:Tetrazoles / Q000633:toxicity; D053773:Transforming Growth Factor beta1 / Q000032:analysis* / Q000097:blood; D014633:Valine / Q000031:analogs & derivatives / Q000633:toxicity; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D007527:Isoenzymes; D013777:Tetrazoles; D053773:Transforming Growth Factor beta1; D015675:Osteocalcin; D000068756:Valsartan; C000605510:ACP5 protein, human; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D014633:Valine; D000077333:Telmisartan