Abstract P101: eNOS is Up-regulated by Whole Body Periodic Acceleration (pGz) in Mice
pGz is a method which moves the body in a sinusoidal head to foot motion, adding pulses to the circulation and increasing shear stress to the endothelium. pGz activates the eNOS pathway and increases release of eNO and its enzyme (eNOS). We have established optimum frequencies of pGz for eNO production in humans, swine, sheep and rats based upon the change of dichrotic notch (DN) and a/b ratio of the arterial pulse waveform and/or eNOS protein levels. Since eNO dilates small resistance vessels, the DN moves downward on the pulsewaveform due to delayed wave reflection, which can be quantified by a/b ratios where ‘a’ is the amplitude of the pulse and ‘b’ the height of the DN. Increase of a/b implies vasodilatation. We sought to determine; whether pGz as applied to mice releases eNO as indicated by a/b ratio, optimal frequency for pGz, and time course for up-regulation of eNOS. In anesthetized mice, we measured a/b ratios as a function of frequency. Three frequencies of pGz with g held constant at ±0.3 were studied. The optimal frequency which produced the largest increase in a/b was a frequency of 480 cpm. This frequency was applied daily for one hour to awake unsedated mice in a restrainer, over a period of 4 days, along with a time control group (CONT). Myocardial tissue was harvested 24 hrs later to assess eNOS using an immunoblotting. eNOS results in graph (mean±sd). pGz applied to mice releases physiologically significant amounts of eNO and activates eNOS. pGz is a feasible approach to up-regulate eNOS and release NO in mice, providing a tool for investigation of mechanisms for its protective effects in clinically relevant models of ischemia reperfusion injury and transgenic mouse models.