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Contribution of the NO-GC isoforms to airway responsiveness

Hyperreactivity of airways to bronchoconstrictive agents is a common feature of reactive airway diseases. In addition to its established role on vascular smooth muscle tone, the NO/cGMP pathway is also expected to balance the contractile responses of airway smooth muscle. The NO-sensitive guanylyl cyclase (NO-GC) which forms cyclic GMP in response to NO holds a key position in this pathway and exists in two isoforms, NO-GC1 and NO-GC2, which both have been identified in bronchial and pulmonary blood vessels smooth muscle.

Here we determined the contribution of the NO-GC isoforms to the regulation of airway resistance. Airway resistance was determined in a whole body plethysmography chamber in conscious mice deficient in either NO-GC1 or NO-GC2 in response to methacholine and serotonine inhalation. L-NAME was applied to NO-GC KOs to analyse the effect mediated by the remaining NO-GC isoform and to WT to inhibit both isoforms to see a possible synergistic or antagonistic action. The ganglionic blocker hexamethonium was use to differentiate bronchial and neuronal pathways.

Preliminary results indicate that both NO-GC isoforms contribute to airway responsiveness.

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Correspondence to Evanthia Mergia.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Mergia, E., Köhler-Bachmann, S., Puschkarow, M. et al. Contribution of the NO-GC isoforms to airway responsiveness. BMC Pharmacol Toxicol 16 (Suppl 1), A67 (2015).

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