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1 Department of Critical Care and Pulmonary Services, University of Athens, Athens, Greece; Department of Pharmacy, University of Patras, Patras, Greece
2 Department of Pharmacy, University of Patras, Patras, Greece
3 Institute for Biomedical Research, Academy of Athens, Athens, Greece
4 Department of Critical Care and Pulmonary Services, University of Athens, Athens, Greece
* To whom correspondence should be addressed. E-mail: apapapet{at}upatras.gr.
Soluble guanylyl cyclase is an enzyme highly expressed in the lung that generates cGMP contributing to airway smooth muscle relaxation. To determine whether the bronchoconstriction observed in asthma is accompanied by changes in soluble guanylyl cyclase expression, we used a well-established murine model of allergic asthma. Histological and biochemical analyses confirmed the presence of inflammation in the lungs of mice sensitized and challenged with ovalbumin (OVA). Moreover, mice sensitized and challenged with OVA exhibited airway hyperreactivity to methacholine inhalation. Steady-state mRNA levels for all soluble guanylyl cyclase subunits (
1, 2 and 
1) were reduced in the lungs of mice with allergic asthma by 60-80 %, as estimated by real-time PCR. These changes in mRNA were paralleled by changes at the protein level: 1, 2 and 1 expression was reduced by 50-80% as determined by western blotting. Reduced 1 and 1 expression in bronchial smooth muscle cells was demonstrated by immunohistochemistry. To study if soluble guanylyl cyclase inhibition mimics the airway hyperreactivity seen in asthma, naive mice we treated with a selective sGC inhibitor. Indeed, in mice receiving ODQ the methacholine dose-response was shifted to the left. We conclude that soluble guanylyl cyclase expression is reduced in experimental asthma contributing to the observed airway hyperreactivity.
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