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Contribution of the NO-GC isoforms to airway responsiveness
BMC Pharmacology and Toxicology volume 16, Article number: A67 (2015)
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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Mergia, E., Köhler-Bachmann, S., Puschkarow, M. et al. Contribution of the NO-GC isoforms to airway responsiveness. BMC Pharmacol Toxicol 16, A67 (2015). https://0-doi-org.brum.beds.ac.uk/10.1186/2050-6511-16-S1-A67
- Airway Smooth Muscle
- Contractile Response
- Airway Resistance
- Guanylyl Cyclase