Endothelin subtype A receptor antagonist induces osteopenia in growing rats

Previous studies suggested that endothelin (ET) peptides are involved in bone metabolism. We examined the effects of long-term blockade of the ET(A) receptor, a receptor subtype primarily involved in the anabolic actions of ET, on bone mineral status in growing rats. Eight-week-old rats injected intraperitoneally with FR139317 50 mg/kg body weight, a specific ET(A) receptor antagonist, for 2 or 4 weeks were compared with control rats injected with vehicle only. Treatment with FR139317 caused a significant decrease in bone mass in the lumbar spine as determined by dual-energy x-ray absorptiometry (DXA). FR139317-induced osteopenia was associated with a significant decrease in the serum osteocalcin concentration but no change in the urinary excretion of pyridinium cross-links of collagen. Our findings indicate that long-term blockade of the ET(A) receptor reduces bone formation and induces osteopenia in growing rats. Our results suggest that ET produced by vascular endothelial cells plays an important role in bone growth and metabolism in vivo.