Nitric oxide-mediated vasodilation in human bone

Abstract

Objective: Regulation of blood flow to bone is critical but poorly understood, particularly in humans. This study aims to determine whether nitric oxide (NO), a major regulator of vascular tone to other tissues, contributes also to the regulation of blood flow to bone.

Methods: In young healthy adults (n = 16, 8F, 8M), we characterized NO-mediated vasodilation in the tibia in response to sublingual nitroglycerin and contrasted it to lower leg. Blood flow responses were assessed in supine individuals by continuously measuring tibial total hemoglobin (tHb) via near-infrared spectroscopy and lower leg blood flow (LBF) as popliteal flow velocity via Doppler ultrasound in the same leg.

Results: LBF increased by Δ9.73 ± 0.66 cm/s and peaked 4.4 min after NO administration and declined slowly but remained elevated (Δ3.63 ± 0.60 cm/s) at 10 min. In contrast, time to peak response was longer and smaller in magnitude in the tibia as tHb increased Δ2.08 ± 0.22 μM and peaked 5.3 min after NO administration and declined quickly but remained elevated (Δ0.87±0.22 μM) at 10 min (p = .01).

Conclusions: In young adults, the tibial vasculature demonstrates robust NO-mediated vasodilation, but tHb is delayed and diminishes faster compared to LBF, predominately reflective of skeletal muscle responses. Thus, NO-mediated vasodilation in bone may be characteristically different from other vascular beds.

Trial registration: ClinicalTrials.gov NCT04083794.

Keywords: near-infrared spectroscopy; nitric oxide-mediated vasodilation; tibial bone vasculature.

Figure 1.

Non-invasive NIRS device for measuring tibial bone blood content as oxy-, deoxy-, and total hemoglobin.

Figure 2.

NO-mediated vasodilation in lower leg and tibial bone vasculature. Group average response to sublingual nitroglycerin. ΔMAP, mean arterial pressure change; ΔLBF, popliteal artery blood flow velocity change; tHb, tibial bone total hemoglobin change. All changes are relative to resting baseline. Data are presented as mean + SE. n = 16 (8M, 8F).

Figure 3.

Maximum flow (left) and time to maximum flow (right) response to sublingual nitroglycerin in the lower leg (ΔLBF) and tibial bone (tHb) in N = 8 males and N = 8 females. Notice the different scale of ΔLBF compared to tibial tHb. * p < 0.01, F, Time to max tibia vs. lower leg.