This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200601-048OCv1 174/7/743    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Abraham, W. M. Articles by Sackner, M. A. Search for Related Content PubMed PubMed Citation Articles by Abraham, W. M. Articles by Sackner, M. A.

Whole-Body Periodic Acceleration Modifies Experimental Asthma in Sheep

Division of Pulmonary Disease and Critical Care Medicine, Miller School of Medicine, University of Miami at Mount Sinai Medical Center; and Department of Neonatology, Mount Sinai Medical Center, Miami Beach, Florida

Correspondence and requests for reprints should be addressed to William M. Abraham, Ph.D., Department of Research, Mount Sinai Medical Center, 4300 Alton Road, Miami Beach, FL 33140. E-mail: abraham{at}msmc.com

Rationale: 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.

Objectives: 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-B (NF-B) 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-B 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.

Conclusion: Whole-body pGz modulates allergen-induced airway responses in allergic sheep.

Key Words: animal models • asthma therapy • nitric oxide • noninvasive periodic acceleration

This article has been cited by other articles:

				W. C. Moore and S. P. Peters Update in Asthma 2006 Am. J. Respir. Crit. Care Med., April 1, 2007; 175(7): 649 - 654. [Full Text] [PDF]