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  • Meeting abstract
  • Open Access

Contribution of the NO-GC isoforms to airway responsiveness

  • 1Email author,
  • 2,
  • 2 and
  • 1
BMC Pharmacology and Toxicology201516 (Suppl 1) :A67

https://doi.org/10.1186/2050-6511-16-S1-A67

  • Published:

Keywords

  • Airway Smooth Muscle
  • Contractile Response
  • Airway Resistance
  • Methacholine
  • Guanylyl Cyclase

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.

Authors’ Affiliations

(1)
Institute of Pharmacology, Ruhr-University Bochum, Bochum, Germany
(2)
Department of Experimental Pneumology, Ruhr-University Bochum, Bochum, Germany

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