Figure 1. Airway relaxation induced by NO donors and its enhancement by ZAP. (A) Phase-contrast images showing the appearance of an airway in a lung slice (1) at rest, (2) after 8 min of stimulation with 0.1 µM 5-HT, (3) after relaxation induced by 10 µM NOC-5, and (4) after further relaxation induced by NOC-5 in the presence of 10 µM ZAP (image times indicated by arrows in B). (B, black trace) The change in the cross-sectional area of the lumen of an airway with respect to time showing the contraction in response to 5-HT and subsequent relaxation induced by NOC-5 in the absence or presence of ZAP (top bars). The airway contracted in response to 5-HT and relaxed in response to NOC-5. The effect of NOC-5 was biphasic and quickly reversed upon NOC-5 washout. ZAP alone had little effect on airway contraction but increased the relaxing effect of NOC-5. The effect of ZAP was reversed after washout. (B, gray trace) The relaxation of 5-HT–contracted airways induced by 50 µM SNAP. (C) Concentration dependence of airway relaxation induced by NOC-5 in the absence (black traces) or presence (gray traces) of ZAP. Relaxation was measured as the increase in lumen area after 30 s (peak; dashed lines, circles) or after 10 min (sustained; continuous lines, squares) of NOC-5 exposure from experiments shown in B. In control experiments with 5-HT alone (not depicted), we observed a slow but continued increase in airway contraction of 2.1 ± 1.3 and 1.6 ± 1.1% during the time periods of 12–22 min and 48–58 min, which correspond to the exposure times for NOC-5 or NOC-5/ZAP. Consequently, we corrected the measurements of sustained relaxation at these times by adding the corresponding additional contraction. Each point represents the mean ± SE from at least five different slices from at least two mice. A movie of these data is shown in Video 1.
Figure 1.

Airway relaxation induced by NO donors and its enhancement by ZAP. (A) Phase-contrast images showing the appearance of an airway in a lung slice (1) at rest, (2) after 8 min of stimulation with 0.1 µM 5-HT, (3) after relaxation induced by 10 µM NOC-5, and (4) after further relaxation induced by NOC-5 in the presence of 10 µM ZAP (image times indicated by arrows in B). (B, black trace) The change in the cross-sectional area of the lumen of an airway with respect to time showing the contraction in response to 5-HT and subsequent relaxation induced by NOC-5 in the absence or presence of ZAP (top bars). The airway contracted in response to 5-HT and relaxed in response to NOC-5. The effect of NOC-5 was biphasic and quickly reversed upon NOC-5 washout. ZAP alone had little effect on airway contraction but increased the relaxing effect of NOC-5. The effect of ZAP was reversed after washout. (B, gray trace) The relaxation of 5-HT–contracted airways induced by 50 µM SNAP. (C) Concentration dependence of airway relaxation induced by NOC-5 in the absence (black traces) or presence (gray traces) of ZAP. Relaxation was measured as the increase in lumen area after 30 s (peak; dashed lines, circles) or after 10 min (sustained; continuous lines, squares) of NOC-5 exposure from experiments shown in B. In control experiments with 5-HT alone (not depicted), we observed a slow but continued increase in airway contraction of 2.1 ± 1.3 and 1.6 ± 1.1% during the time periods of 12–22 min and 48–58 min, which correspond to the exposure times for NOC-5 or NOC-5/ZAP. Consequently, we corrected the measurements of sustained relaxation at these times by adding the corresponding additional contraction. Each point represents the mean ± SE from at least five different slices from at least two mice. A movie of these data is shown in Video 1.

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