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Adenosine-mediated alteration of vascular reactivity and inflammation in a murine model of asthma

Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, West Virginia

Submitted 22 October 2007 ; accepted in final form 26 February 2008

Chronic respiratory disorders such as asthma are believed to be associated with adverse cardiovascular events. We hypothesize that asthmatic inflammation translates into systemic inflammation and alters vascular responses where adenosine (AD) plays an important role. Therefore, this study investigated the effects of aerosolized AD, used to elevate lung AD levels, on vascular reactivity and inflammation in our allergic mouse model of asthma. Balb/c mice were divided into four groups: control (Con), Con + aerosolized AD (Con + AD), allergen sensitized and challenged (Sen), and Sen + aerosolized AD (Sen + AD). The animals were sensitized with ragweed (200 µg ip) on days 1 and 6, followed by 1% ragweed aerosol challenges from days 11 to 13. On day 14, the Con + AD and Sen + AD groups received a single AD aerosol challenge (6 mg/ml) for 2 min, followed by the collection of the aorta and plasma on day 15. Organ bath experiments showed concentration-dependent aortic relaxations to AD in the Con and Con + AD groups, which were impaired in the Sen and Sen + AD groups. Real-time PCR data showed changes in aortic AD receptors (ARs), with the expression of A₁ARs upregulated, whereas the expression of A₂ARs and endothelial nitric oxide synthase genes were downregulated, resulting in an impairment of vasorelaxation in the Sen and Sen + AD groups. The A₁AR antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) reversed the impairment in vasorelaxation observed in the Sen and Sen + AD groups, whereas the A_2BAR antagonist alloxazine inhibited vasorelaxation in all groups. Allergen challenge caused systemic inflammation in allergic mice, with AD aerosol further enhancing it as determined by the inflammatory cytokines profile in plasma. In conclusion, asthmatic mice showed altered vascular reactivity and systemic inflammation, with AD aerosol further exacerbating these effects.

allergen; systemic inflammation

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				A. Nadeem, D. S. Ponnoth, H. R. Ansari, T. P. Batchelor, R. D. Dey, C. Ledent, and S. J. Mustafa A2A Adenosine Receptor Deficiency Leads to Impaired Tracheal Relaxation via NADPH Oxidase Pathway in Allergic Mice J. Pharmacol. Exp. Ther., July 1, 2009; 330(1): 99 - 108. [Abstract] [Full Text] [PDF]