Abstract
To investigate how nitric oxide (NO) induces airway smooth muscle cell (SMC) relaxation, we examined airway contraction, Ca2+ signalling, and Ca2+ sensitivity in mouse lung slices in response to agonists and an NO donor, NOC‐5. In airways contracted with 5‐HT or ACh, NOC‐5 induced a concentration‐dependent relaxation consisting of an initial relaxation followed by partial re‐contraction. Inhibition of cGMP‐specific phosphodiesterases (PDE‐5) with zaprinast increased NOC‐5‐induced relaxation. 8‐Br‐cGMP, a PDE‐resistant analog of cGMP, induced sustained airway relaxation. Agonist‐induced airway contraction was mediated by SMC Ca2+ oscillations and airway relaxation correlated with a NOC‐5‐induced reduction in the frequency of these Ca2+ oscillations. NOC‐5 inhibited the Ca2+ oscillations and contraction triggered by the photolytic release of IP3 in SMCs. However, in Ca2+ permeabilized SMCs, NO only induced a small airway relaxation when the [Ca2+]i was clamped at a high level. We conclude that NO relaxes airway SMCs by decreasing the frequency of Ca2+ oscillations by blocking Ca2+ release via IP3 receptors and not by a major change in Ca2+ sensitivity.
Published Version
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