Vascular dysfunction contributes to the development of osteopenia in hypertensive patients, as decreased blood supply to bones results in tissue damage and dysfunction. The effect of anti-hypertensive medicines on bone mass in hypertensive individuals is inconclusive because of the varied mechanism of their action, and suggests that reducing blood pressure (BP) alone is insufficient to enhance bone mass in hypertension. Pentoxifylline (PTX), a hemorheological drug, improves blood flow by reducing blood viscosity and angiogenesis, also has an osteogenic effect. We hypothesized that improving vascular function is critical to increasing bone mass in hypertension. To test this, we screened various anti-hypertensive drugs for their in vitro osteogenic effect, from which timolol and hydralazine were selected. In adult female spontaneously hypertensive rats (SHRs), timolol and hydralazine did not improve vascular function and bone mass, but PTX improved both. In female SHR animals, PTX restored bone mass, strength and mineralization, up to the level of normotensive control rats. In addition, we observed lower blood vasculature in the femur of adult SHR animals, and PTX restored them. PTX also restored the bone vascular and angiogenesis parameters that had been impaired in OVX SHR compared to sham SHR. This study demonstrates the importance of vascular function in addition to increased bone mass for improving bone health as achieved by PTX without affecting BP, and suggests a promising treatment option for osteoporosis in hypertensive patients, particularly at-risk postmenopausal women.

血管功能障碍会导致高血压患者骨质减少，因为骨骼供血减少会导致组织损伤和功能障碍。抗高血压药物对高血压患者骨量的影响尚无定论，因为其作用机制各不相同，并且表明单独降低血压（BP）不足以增加高血压患者的骨量。己酮可可碱 (PTX) 是一种血液流变药物，通过降低血液粘度和血管生成来改善血流，还具有成骨作用。我们假设改善血管功能对于增加高血压患者的骨量至关重要。为了测试这一点，我们筛选了各种抗高血压药物的体外成骨作用，从中选择了噻吗洛尔和肼屈嗪。在成年雌性自发性高血压大鼠 (SHR) 中，噻吗洛尔和肼屈嗪并不能改善血管功能和骨量，但 PTX 可以改善两者。在雌性 SHR 动物中，PTX 恢复了骨量、强度和矿化，达到正常血压对照大鼠的水平。此外，我们观察到成年 SHR 动物股骨中的血管系统较低，PTX 可以恢复它们。与假 SHR 相比，PTX 还恢复了 OVX SHR 中受损的骨血管和血管生成参数。这项研究证明了除了增加骨量之外，血管功能对于通过 PTX 在不影响血压的情况下改善骨骼健康也很重要，并为高血压患者（尤其是高危绝经后妇女）的骨质疏松症提出了一种有前景的治疗选择。