Abstract 184: Whole Body Periodic Acceleration in Mice Increases Endothelial Nitric Oxide Synthase Gene Transcription
Background: Whole Body Periodic Acceleration (pGz) is a method which moves the body in a sinusoidal head to foot motion, adding pulses to the circulation thereby increasing pulsatile, cyclical shear stress to the endothelium. pGz activates the PI3/Akt eNOS pathway and increases release of eNO and its enzyme Endothelial Nitric Oxide Synthase (eNOS). Optimum frequency of pGz has been established in our laboratory for various animal species and humans. In myocardium, acute phosphorylation of eNOS and protein expression have been shown to occur after a single 1 hr exposure to pGz.
Hypothesis: We tested the hypothesis that repeated exposure to pGz in mice would modify gene transcription of eNOS and determined the time course for decline of eNOS transcription.
Methods: Acclimated awake mice (n=48) where exposed to shear stress at 480 cpm, Gz ± 3mt/sec 2 (pGz) for daily 1 hr sessions at 1, 4, 8 and 14 days or no pGz as control (CONT). Myocardial tissue was harvested 24 hrs after the last treatment for PCR. To determine the time course of decline of eNOS gene transcription a separate group received 4 days of pGz or CONT and tissue was harvested for PCR at 4, 12, 24, 48, 72 hrs.
Results: pGz applied to mice in addition to activating eNOS (via phosphorylation) increases eNOS gene transcription as a function of days of pGz exposure. This transcription reaches a maximum at 8 days. After 4 days of pGz a gradual decrease in eNOS transcription occurs between 24 and 72 hrs.
Conclusions: pGz may be a valuable intervention to up-regulate genetic expression of eNOS for therapeutic purposes.
- © 2010 by American Heart Association, Inc.