The role of sympathetic control in bone vasculature: insights from spinal cord injury.

Abstract

Bone vasculature is richly innervated by an extensive network of sympathetic nerves. However, our understanding of bone blood flow regulation and its contribution to human bone health is limited. Here, we further our previous findings by characterizing bone vascular responses in the absence of sympathetic control - studying individuals with spinal cord injury (SCI), a population with known peripheral sympathetic disruption. We assessed tibial vascular responses to isometric handgrip exercise (IHE) in individuals with SCI (n = 12) and controls (n = 12). When sustained to fatigue, IHE increases perfusion pressure and sympathetic vasoconstriction in the non-active tissues of the legs. During IHE, we measured blood pressure, whole leg blood velocity via ultrasound, and tibial perfusion (as hemoglobin content) via near-infrared spectroscopy. Controls demonstrated active sympathetic vasoconstriction in the whole leg (i.e., increased vascular resistance, arterial pressure/leg blood velocity) and tibia (i.e., decreased hemoglobin). In contrast, SCI individuals demonstrated modest whole leg vasoconstriction with lesser increases in vascular resistance than controls (P<.04). Tibial vasculature evidenced absent or blunted vasoconstriction compared to controls (P<.01), indicated by increasing tibial hemoglobin until plateauing at higher pressure levels. This suggests that, in the absence of sympathetic control, tibial vascular response may involve other regulatory mechanisms like myogenic vasoconstriction. Lastly, we leveraged existent whole-body Dual Energy X-ray Absorptiometry scans in a subgroup of nine individuals with SCI and we found a strong relationship between leg bone mineral density (BMD) and tibial hemoglobin at end of IHE (r2 = 0.67, P<.01). Our findings indicate that in the absence of sympathetic mechanisms, myogenic control may play a compensatory role in regulating blood flow, though to a lesser extent in bone compared to muscle. The close relationship between lesser declines in bone blood content and higher BMD underscores the link between blood flow and bone health.