Low-amplitude pulses to the circulation through periodic acceleration induces endothelial-dependent vasodilatation

Abstract

Low-amplitude pulses to the vasculature increase pulsatile shear stress to the endothelium. This activates endothelial nitric oxide (NO) synthase (eNOS) to promote NO release and endothelial-dependent vasodilatation. Descent of the dicrotic notch on the arterial pulse waveform and a-to- b ratio ( a/ b; where a is the height of the pulse amplitude and b is the height of the dicrotic notch above the end-diastolic level) 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 pGzapplied to rats produced endothelial-dependent vasodilatation and increased NO production, and whether the latter was regulated by the Akt/phosphatidylinositol 3-kinase (PI3K) pathway. Male rats were anesthetized and instrumented, and pGzwas applied. Sodium nitroprusside, NG-nitro-l-arginine methyl ester (l-NAME), and wortmannin (WM; to block Akt/PI3K pathway) were administered to compare changes in a/ b and mean aortic pressure. Descent of the dicrotic notch occurred within 2 s 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, pGzdid not decrease aortic pressure or increase a/ b. WM also abolished the pGzblunting 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 pGzproduces endothelial-dependent vasodilatation due to increased NO in rats, which is mediated via activation of eNOS, in part, by the Akt/PI3K pathway.