Attenuation in Acetylcholine, Nitroprusside, and Phenylephrine‐dependent Change in Blood Flow Contributes to Bone Microvascular Remodeling in Hyperhomocysteinemia

Despite the fact that patients with hyperhomocysteinemia display a variety of bone disease symptoms related to bone weakness surprisingly little is known about mechanisms of bone weakness in hyperhomocysteinemia (HHcy). To begin to address this important question of what causes bone weakness in HHcy, we measured bone density in healthy and heterozygous cystathione synthase deficient mice (CBS+/−) mice by utilizing digital X‐ray scan. We also measured blood flow in tibia bone of healthy and CBS +/− mice by using Lazer Doppler and Ultra Sound flow probe methods in unaltered state and after injection of acetylcholine (Ach), sodium nitroprusside (SNP), bradykinin (BK) and phenylephrine (PE). Lastly, we measured expression of matrix metalloproteinase 9 (MMP‐9) in bone extracts from healthy and CBS mice. We found that bone density, blood flow and vascular reactivity to Ach, SNP, BK and PE in CBS+/− mice are lower than in a healthy group while expression of MMP‐9 is increased. Attenuation of vascular response in CBS+/− to Ach, SP and PE suggests that in HHcy both, endothelium and underlying smooth muscle are affected. The attenuation of PE response suggests alpha 1 adrenergic receptor impairment. Increased levels of MMP‐9 indicate that type IV collagen, a structural component of basal lamina, is degraded at an increased rate in the bone of HHcy mice.