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Previously we showed that neuropeptide Y (NPY), a sympathetic vasoconstrictor neurotransmitter, stimulates endothelial cell migration, proliferation, and differentiation in vitro. Here, we report on NPY’s actions, receptors, and mediators in ischemic angiogenesis. In rats, hindlimb ischemia stimulates sympathetic NPY release (attenuated by lumbar sympathectomy) and upregulates NPY-Y2 (Y2) receptor and a peptidase forming Y2/Y5-selective agonist. Exogenous NPY at physiological concentrations also induces Y5 receptor, stimulates neovascularization, and restores ischemic muscle blood flow and performance. NPY-mediated ischemic angiogenesis is not prevented by a selective Y1 receptor antagonist but is reduced in Y2–/– mice. Nonischemic muscle vascularity is also lower in Y2–/– mice, whereas it is increased in NPY-overexpressing rats compared with their WT controls. Ex vivo, NPY-induced aortic sprouting is markedly reduced in Y2–/– aortas and spontaneous sprouting is severely impaired in NPY–/– mice. NPY-mediated aortic sprouting, but not cell migration/proliferation, is blocked by an antifetal liver kinase 1 antibody and abolished in mice null for eNOS. Thus, NPY mediates neurogenic ischemic angiogenesis at physiological concentrations by activating Y2/Y5 receptors and eNOS, in part due to release of VEGF. NPY’s effectiveness in revascularization and restoring function of ischemic tissue suggests its therapeutic potential in ischemic conditions

Changes in the structure of motor variability during practicing a bimanual pointing task were investigated using the framework of the uncontrolled manifold (UCM) hypothesis. The subjects performed fast and accurate planar movements with both arms, one moving the pointer and the other moving the target. The UCM hypothesis predicts that joint kinematic variability will be structured to selectively stabilize important task variables. This prediction was tested with respect to selective stabilization of the trajectory of the endpoint of each arm (unimanual control hypotheses) and with respect to selective stabilization of the timecourse of the vectorial distance between the target and the pointer tip (bimanual control hypothesis). Components of joint position variance not affecting and affecting a mean value of a selected variable were computed at each 10% of normalized movement time. The ratio of these two components ( R(V)) served as a quantitative index of selective stabilization. Both unimanual control hypotheses and the bimanual control hypothesis were supported both prior to and after practice. However, the R(V) values for the bimanual control hypothesis were significantly higher than for either of the unimanual control hypothesis, suggesting that the bimanual synergy was not simply a simultaneous execution of two unimanual synergies. After practice, an improvement in both movement speed and accuracy was accompanied by counterintuitive changes in the structure of kinematic variability. Components of joint position variance affecting and not affecting a mean value of a selected variable decreased, but there was a significantly larger drop in the latter when applied on each of the three selected task variables corresponding to the three control hypotheses. We conclude that the UCM hypothesis allows quantitative assessment of the degree of stabilization of selected performance variables and provides information on changes in the structure of a multijoint synergy that may not be reflected in its overall performance.

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