Abstract
Periodic acceleration (pGz) stimulates NO release from endothelial nitric oxide synthase (eNOS) through pulsatile shear stress (Adams. Ann.Biomed.Engineer.2003;31:1337). We showed that: a) pretreatment with pGz significantly blunts the early (EAR) and blocks the late (LAR) allergen-induced airway responses in allergic sheep; b) pGz-induced protection is lost if the eNOS inhibitor, L-NAME, is given 30 min before pGz treatment and c) initiating pGz 2h after antigen challenge still blocks the LAR (Abraham. Am.J.Respir.Crit Care Med.2004, in press). NF-kB is a transcription factor for inflammatory cytokines involved in the LAR. There are reports that eNOS generated NO suppresses NF-kB activity (Blais.J.Neuropathol. Exp.Neurol.2001;60:893). To determine if pGz suppresses NF-kB activity thereby affecting antigen-induced airway responses, we performed bronchoalveolar lavage 6h after antigen challenge and measured free p65 levels in lavage cell nuclear extracts (an indicator of NF-kB activation) by ELISA. Peak LAR (% increase over baseline) in control, pGz-treated and L-NAME+pGz treated sheep (all n=6) were 118±2%, 21±4% and 130±4%, respectively. Levels of p65/106 cells were 1.9- and 1.8-fold higher in the control and L-NAME+pGz groups (both p<0.05) when compared to pGz treated animals. Therefore, pGz stimulates eNOS and increases NO throughout the body, which can block NF-kB –mediated inflammation.