Bone Abstracts (2013) 1 OC6.4 | DOI: 10.1530/boneabs.01.OC6.4

Inhibition of PTH-induced vasorelaxation modulates its anabolic action

Stephanie Gohin1,2, Chantal Chenu3, Andrew Pitsillides3, Timothy Arnett2 & Massimo Marenzana1,4

1Imperial College London, London, UK; 2University College London, London, UK; 3Royal Veterinary College, London, UK; 4University of Oxford, Oxford, UK.

The relationship between bone formation and blood flow is unclear. Recently, PTH was reported to activate production of nitric oxide (NO), a potent vasorelaxing agent, in endothelial cells and we and others have confirmed a strong vasorelaxing action of PTH in vivo in the mouse. Here, we tested the hypothesis that a potent NO synthase inhibitor (L-NAME: NG-nitro-L-arginine methyl ester) may alter the effect of intermittent PTH (iPTH) on bone architecture by blocking its vasodilatory effect.

Four groups of male BALB/c mice (n=8 per group) were daily injected subcutaneously for 28 days PBS, PTH(1–34) alone (80 μg/kg per day), PTH plus L-NAME (30 μg/kg per day, i.p.) or L-NAME alone. Hind limb perfusion was measured by laser Doppler imaging. Bone architecture in the femur was imaged by micro-CT ex vivo.

PTH increased lower limb blood flow by ≥30% within 10 min of injection, an effect that was sustained over the 20 min recording period, compared to placebo (P<0.001). Co-treatment with L-NAME abolished the action of PTH but L-NAME alone had no effect. These acute effects were not attenuated over 28 days repetition. No chronic effects of iPTH or L-NAME were evident when blood flow was monitored 24 h after the last injection.

As expected, iPTH increased femoral cortical thickness (+17%; P<0.001) and trabecular thickness in the secondary spongiosa of the distal femoral metaphysis (+26%; P<0.001). Co-treatment with L-NAME decreased trabecular bone volume (P<0.01) by reducing trabecular number and increasing structural model index, compared to PTH alone.

In conclusion, PTH induced robust, acute increases in limb blood flow that were blocked by L-NAME. The anabolic action of iPTH was also blocked by L-NAME in the trabecular but not in the cortical compartment of the femur. These results suggest that the bone anabolic action of PTH could involve in part NO-mediated vasorelaxation.

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