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

Abstract

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 mug 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 A(1)ARs upregulated, whereas the expression of A(2)ARs and endothelial nitric oxide synthase genes were downregulated, resulting in an impairment of vasorelaxation in the Sen and Sen + AD groups. The A(1)AR antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) reversed the impairment in vasorelaxation observed in the Sen and Sen + AD groups, whereas the A(2B)AR 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.

• Authors: Dovenia S Ponnoth, Ahmed Nadeem, S Jamal Mustafa
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 294 Issue 5 Pg. H2158-65 (May 2008) ISSN: 0363-6135 [Print] United States
• PMID: 18310516 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Allergens
• Flavins
• Inflammation Mediators
• Plant Proteins
• Receptor, Adenosine A1
• Receptor, Adenosine A2A
• Receptor, Adenosine A2B
• Vasodilator Agents
• Xanthines
• isoalloxazine
• 1,3-dipropyl-8-cyclopentylxanthine
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Nos3 protein, mouse
• Adenosine
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Adenosine (administration & dosage, metabolism)
• Administration, Inhalation
• Allergens
• Ambrosia (immunology)
• Animals
• Aorta (drug effects, enzymology, immunology, metabolism, physiopathology)
• Asthma (immunology, metabolism, physiopathology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Flavins (pharmacology)
• Inflammation (blood, immunology, metabolism, physiopathology)
• Inflammation Mediators (blood)
• Lung (metabolism, physiopathology)
• Male
• Mice
• Mice, Inbred BALB C
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Nitric Oxide Synthase Type III
• Plant Proteins (immunology)
• Receptor, Adenosine A1 (genetics, metabolism)
• Receptor, Adenosine A2A (genetics, metabolism)
• Receptor, Adenosine A2B (genetics, metabolism)
• Vasodilation (drug effects)
• Vasodilator Agents (pharmacology)
• Xanthines (pharmacology)