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

Abstract

Uryash A, Wu H, Bassuk J, Kurlansky P, Sackner MA, Adams JA. Low-amplitude pulses to the circulation through periodic acceleration induces endothelial-dependent vasodilatation. J Appl Physiol 106: 1840 -1847, 2009. First published March 26, 2009 doi:10.1152/japplphysiol.91612.2008.-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 (pG z) (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 pG z applied 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 pG z was applied. Sodium nitroprusside, N G -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 pG z. 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 pG z. In the presence of WM, pGz did not decrease aortic pressure or increase a/b. WM also abolished the pG z blunting effect on blood pressure and a/b of L-NAME-treated animals. eNOS expression was increased in aortic tissue after pG z. This study indicates that addition of low-amplitude pulses to circulation through pG z produces endothelial-dependent vasodilatation due to increased NO in rats, which is mediated via activation of eNOS, in part, by the Akt/PI3K pathway. vascular resistance; N G -nitro-L-arginine methyl ester, wortmannin; nitric oxide ADDED LOW-AMPLITUDE PULSES to the vasculature were generated with periodic acceleration (pG z ). pG z is produced by a motorized platform that repetitively moves the horizontally oriented body sinusoidally in a head to foot direction. Inertia of fluid as the body accelerates and decelerates adds a small-amplitude pulse to the circulation that is superimposed on the natural pulse, increasing pulsatile shear stress to the endothelium (3, 6, 7). In large-animal models, increased pulsatile shear stress activates endothelial nitric oxide (NO) synthase (eNOS) to release NO into the circulation, which, in turn, induces endothelial-dependent pulmonary and systemic vasodilatation, as well as increasing organ blood flows (3,5,6). pG z applied to anesthetized swine increases serum nitrite, which is ...

Preconditioning with periodic acceleration (pGz) provides second window of cardioprotection

“…As the body accelerates and decelerates, low amplitude pulses are added to the circulation as a function of platform frequency thereby increasing pulsatile shear stress to the endothelium (Adams, 2006;Sackner et al, 2005;Uryash et al, 2009). pGz through its increase of pulsatile shear stress upregulates eNOS and increases its phosphorylation p-eNOS (Ser 1177) Wu et al, 2009).…”

“…pGz through its increase of pulsatile shear stress upregulates eNOS and increases its phosphorylation p-eNOS (Ser 1177) Wu et al, 2009). eNOS (Ser 1177) phosphorylation after pGz is responsible for shear stress dependent vasodilatation and subsequent increased nitric oxide release into the circulation (Adams et al, 2003;Hutcheson and Griffith, 1991;Li et al, 2005;Uryash et al, 2009). pGz applied to rats has been shown to produce vasodilatation, increase eNOS expression and increases its phosphorylation Wu et al, 2009).…”

Whole Body Periodic Acceleration (pGz) Improves Survival and Allows for Resuscitation in a Model of Severe Hemorrhagic Shock in Pigs

“…pGz induces pulsatile shear stress to the vascular endothelium and has also been shown to increase eNO and eNOS in several animal species and humans [2,3,[5][6][7][8][56][57][58][59], which are in large part the basis for the observed survival, decreased oxygen consumption, and better regional microvascular blood flow during hemorrhage observed in the present study.…”

“…Whole body periodic acceleration (pGz), the repetitive, sinusoidal motion of the body in a head-foot direction, increases pulsatile shear stress on the vascular endothelium thereby stimulating increased release of endothelial derived nitric oxide (eNO), prostacyclin and adrenomedullin into the circulation [1][2][3][4][5][6][7][8]. In models of whole body ischemia reperfusion injury with electrically induced ventricular fibrillation, pGz performed prior to, during, and after ventricular fibrillation has been shown to ameliorate indices of myocardial dysfunction, tissue injury, and the surge of inflammatory and oxidative stress biomarkers upon reperfusion [1,[9][10][11][12].…”

Multi-scale modeling of hemodynamics in the cardiovascular system

“…Blood flow in microcirculation is pulsatile in terms of pressure and pulse wave velocity (PWV) [43], in which pulsatility has wide-ranging physiological consequences [44][45][46], and non-pulsatile flow is observed to be related to dysfunctions of micro-vascular systems [47][48][49]. Compared with steady models of microcirculation that are based on steady state concepts [50][51][52], dynamic models [53,54] may be capable of exploring pulse wave propagation in microcirculation.…”