Whole-body periodic acceleration modifies experimental asthma in sheep.
BACKGROUND
Nitric oxide is released from vascular endothelium in response to increased pulsatile shear stress. Nitric oxide inhibits mast cell activation and is antiinflammatory and therefore might be protective in asthma.


OBJECTIVE
We determined if a noninvasive motion platform that imparts periodic sinusoidal inertial forces to the whole body along the spinal axis (pGz) causing release of endothelial nitric oxide modulates experimental asthma in sheep.


METHODS
Allergic sheep were untreated (control) or were treated with pGz alone or after receiving intravenously the nitric oxide synthase inhibitor N(w)-nitro-L-arginine methyl ester (L-NAME) before aerosol challenge with Ascaris suum, and the effect on antigen-induced airway responses was determined. Bronchoalveolar lavage cells obtained 6 h after antigen challenge were analyzed for nuclear factor-kappaB (NF-kappaB) activity in the respective groups.


RESULTS
pGz treatment for 1 h before antigen challenge reduced the early airway response and blocked the late airway response but did not prevent the antigen-induced airway hyperresponsiveness 24 h after challenge. Administration of L-NAME before pGz completely reversed this protection, whereas L-NAME alone did not affect the antigen-induced responses. NF-kappaB activity was 1.9- and 1.8-fold higher in the control and L-NAME + pGz groups, respectively, compared with pGz-treated animals. Extending the pGz treatment to twice daily for 3 d and then 1 h before antigen challenge blocked the early and late airway responses, the 24-h airway hyperresponsiveness, and the airway inflammatory cell response.


CONCLUSIONS
Whole-body pGz modulates allergen-induced airway responses in allergic sheep.
Abraham
William M
WM
Division of Pulmonary Disease and Critical Care Medicine, University of Miami at Mount Sinai Medical Center, Miami Beach, FL 33140, USA. abraham@msmc.com
Ahmed
Ashfaq
A
Serebriakov
Irakli
I
Lauredo
Isabel T
IT
Bassuk
Jorge
J
Adams
Jose A
JA
Sackner
Marvin A
MA
D000054:Acceleration; D000818:Animals; D000947:Antigens, Helminth; D017165:Ascaris suum / Q000276:immunology; D001249:Asthma / Q000378:metabolism*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D012756:Sheep; D013314:Stress, Mechanical
D000947:Antigens, Helminth; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester