Low amplitude pulses to the vasculature increases pulsatile shear stress to the endothelium. This activates endothelial nitric oxide synthase (eNOS) to promote nitric oxide (NO) release and endothelial dependent vasodilatation. Descent of the dicrotic notch on the arterial pulse waveform and a/b ratio, reflects vasodilator (increased a/b) and vasoconstrictor effects (decreased a/b) due to NO level change Periodic acceleration (pGz)(motion of the supine body head to foot on a platform) provides systemic additional pulsatile shear stress. The purpose of this study was to determine whether or not pGz applied to rats produced endothelial dependent vasodilatation, increased NO production and, whether the latter was regulated by the Akt/PI3K pathway. Male rats were anesthetized, instrumented and pGz applied. Sodium nitroprusside (SNP), L-NAME, and Wortmannin (WM, to block Akt/PI3K pathway) were administered to compare changes in a/b ratio and mean aortic pressure. Descent of the dicrotic notch occurred within two seconds of initiating pGz. Dose dependent increase of a/b and decrease of mean aortic pressure took place with SNP. L-NAME, produced a dose dependent rise in mean aortic pressure and decrease of a/b which was blunted with pGz. In the presence of WM, pGz did not decrease aortic pressure or increase a/b. WM also abolished the pGz blunting effect on blood pressure and a/b of L-NAME treated animals. eNOS expression was increased in aortic tissue after pGz. This study indicates that addition of low amplitude pulses to circulation through pGz produces endothelial dependent vasodilatation due to increased NO in rats which is mediated via activation of eNOS in part by the Akt/PI3K pathway.