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Comparison of Single-Session Dose Response Effects of Whole Body Vibration on Spasticity and Walking Speed in Persons with Spinal Cord Injury
Spasticity affects approximately 65% of persons with spinal cord injury (SCI) and negatively impacts function and quality of life. Whole body vibration (WBV) appears to reduce spasticity and improve walking function; however, the optimal dose (frequency/duration) is not known. We compared single-session effects of four different WBV frequency/duration dose conditions on spasticity and walking speed, in preparation for a planned multi-session study. Thirty-five participants with motor-incomplete SCI received four different doses of WBV: high frequency (50Â Hz)/short duration (180Â s), high frequency/long duration (360Â s), low frequency (30Â Hz)/short duration, and low frequency/long duration, plus a control intervention consisting of sham electrical stimulation. In all conditions, participants stood on the WBV platform for 45-s bouts with 1Â min rest between bouts until the requisite duration was achieved. The frequency/duration dose order was randomized across participants; sessions were separated by at least 1Â week. Quadriceps spasticity was measured using the pendulum test at four time points during each session: before, immediately after, 15Â min after, and 45Â min after WBV. Walking speed was quantified using the 10-m walk test at three time points during each session: baseline, immediately after, and 45Â min after WBV. In the full group analysis, no frequency/duration combination was significantly different from the sham-control condition. In participants with more severe spasticity, a greater reduction in stretch reflex excitability was associated with the high frequency/long duration WBV condition. The sham-control condition was associated with effects, indicating that the activity of repeated sitting and standing may have a beneficial influence on spasticity.
NCT02340910 (assigned 01/19/2015)
Angiotensin II-induced vascular endothelial dysfunction through RhoA/Rho kinase/p38 mitogen-activated protein kinase/arginase pathway
Enhanced vascular arginase activity impairs endothelium-dependent vasorelaxation by decreasing l-arginine availability to endothelial nitric oxide (NO) synthase, thereby reducing NO production. Elevated angiotensin II (ANG II) is a key component of endothelial dysfunction in many cardiovascular diseases and has been linked to elevated arginase activity. We determined signaling mechanisms by which ANG II increases endothelial arginase function. Results show that ANG II (0.1 μM, 24 h) elevates arginase activity and arginase I expression in bovine aortic endothelial cells (BAECs) and decreases NO production. These effects are prevented by the arginase inhibitor BEC (100 μM). Blockade of ANG II AT1 receptors or transfection with small interfering RNA (siRNA) for Gα12 and Gα13 also prevents ANG II-induced elevation of arginase activity, but siRNA for Gαq does not. ANG II also elevates active RhoA levels and induces phosphorylation of p38 MAPK. Inhibitors of RhoA activation (simvastatin, 0.1 μM) or Rho kinase (ROCK) (Y-27632, 10 μM; H1152, 0.5 μM) block both ANG II-induced elevation of arginase activity and phosphorylation of p38 MAPK. Furthermore, pretreatment of BAECs with p38 inhibitor SB-202190 (2 μM) or transfection with p38 MAPK siRNA prevents ANG II-induced increased arginase activity/expression and maintains NO production. Additionally, inhibitors of p38 MAPK (SB-203580, 5 μg·kg−1·day−1) or arginase (ABH, 8 mg·kg−1·day−1) or arginase gene knockout in mice prevents ANG II-induced vascular endothelial dysfunction and associated enhancement of arginase. These results indicate that ANG II increases endothelial arginase activity/expression through Gα12/13 G proteins coupled to AT1 receptors and subsequent activation of RhoA/ROCK/p38 MAPK pathways leading to endothelial dysfunction