Prevention of osteoporosis by angiotensin-converting enzyme inhibitor in spontaneous hypertensive rats.
A recent analysis of clinical studies suggests that angiotensin-converting enzyme (ACE) inhibitors might reduce bone fractures. In this study, we examined whether an ACE inhibitor might attenuate osteoporosis in a hypertensive rat model. In spontaneous hypertensive rats (SHRs), estrogen deficiency induced by ovariectomy (OVX) resulted in a significant increase in osteoclast activation as assessed by the tartrate-resistant acid phosphatase (TRAP) activity in the tibia, accompanied by a significant decrease in bone density evaluated by dual-energy X-ray absorptiometry and an increase in urinary deoxypyridinoline. Treatment with an ACE inhibitor, imidapril, attenuated OVX-induced decrease in bone density and increase in TRAP activity and urinary deoxypyridinoline. As ACE inhibitors possess the effects of blockade of the renin-angiotensin system (RAS) and activation of the bradykinin-nitric oxide pathway, we examined the contribution of both pathways in an OVX-induced osteoporosis model. Administration of nitro-L-arginine methylester (L-NAME) did not alter TRAP activity, urinary deoxypyridinoline or bone density, whereas the administration of a subpressor dose of angiotensin II accelerated the increase in TRAP activity in the tibia, accompanied by a significant decrease in bone density and an increase in urinary deoxypyridinoline. Thus, ACE inhibitors prevented osteoporosis, probably because of the inhibition of RAS, but not of nitric oxide. Overall, ACE inhibitors attenuated osteoporosis in a hypertensive rat model through the blockade of RAS.
Shimizu
Hideo
H
Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Nakagami
Hironori
H
Osako
Mariana Kiomy
MK
Nakagami
Futoshi
F
Kunugiza
Yasuo
Y
Tomita
Tetsuya
T
Yoshikawa
Hideki
H
Rakugi
Hiromi
H
Ogihara
Toshio
T
Morishita
Ryuichi
R
D015502:Absorptiometry, Photon; D000135:Acid Phosphatase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D050071:Bone Density Conservation Agents; D001842:Bone and Bones / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D048289:Imidazolidines / Q000627:therapeutic use; D007527:Isoenzymes / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010010:Osteoclasts / Q000187:drug effects; D010024:Osteoporosis / Q000517:prevention & control*; D010052:Ovariectomy; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects; D000071681:Tartrate-Resistant Acid Phosphatase
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004791:Enzyme Inhibitors; D048289:Imidazolidines; D007527:Isoenzymes; C065166:imidapril; D019001:Nitric Oxide Synthase; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D019331:NG-Nitroarginine Methyl Ester