Prevention of osteoporosis by angiotensin-converting enzyme inhibitor in spontaneous hypertensive rats

Abstract

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.

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel

“…Such inhibition is partly explained by cilnidipine's sympatholytic action mediated by the N-type calcium channel blockade with a reduction in renin secretion by juxtaglomerular cells through renal sympathetic innervation. Because the inhibition of renin-angiotensin system with angiotensin receptor blockers and angiotensin-converting enzyme inhibitors in experimental models prevented osteoporosis in ovariectomy-induced bone loss, 22,34,35 both the inhibition of renin-angiotensin system and the adrenergic stimulation by cilnidipine might have cumulative benefits on bone metabolism.…”

Estrogen Inhibits Vascular Calcification via Vascular RANKL System

“…Bone density measurements were performed by dual-energy x-ray absorptiometry (GE-Lunar DPX-IQ; Madison, Wis) and microcomputed tomography (x-ray computed tomography system, SMX-100CT-SV; Shimazu, Osaka, Japan) and software TRI/3D-BON (RATOC System Engineering Co Ltd, Tokyo, Japan) as described previously. 23 …”

Involvement of the Skeletal Renin-Angiotensin System in Age-Related Osteoporosis of Ageing Mice

“…2,6,7,9) Epidemiological studies have reported the benefit of such antihypertensive drugs as ACE inhibitors and angiotensin II receptor blockers (ARB) for increasing the bone mass and decreasing the risk of bone fractures. 10,11) We therefore hypothesized that bone RAS might be a local regulating system for bone metabolism.…”