Analysis and Design of Stimulus Response Curves of E. coli

To determine whether the inhibition of nitric oxide (NO) synthesis attenuates thermally induced obstruction, we had 10 asthmatic volunteers perform isocapnic hyperventilation with frigid air after inhaling 1 mg of N G-monomethyl-l-arginine (l-NMMA) or isotonic saline in a blinded fashion. The challenges were identical in all respects, and there were no differences in baseline lung function [1-s forced expiratory volume (FEV1); saline 2.8 ± 0.3 liters, l-NMMA 2.9 ± 0.3 liters; P = 0.41] or prechallenge fractional concentration of nitric oxide in the exhaled air (FeNO) [saline 23 ± 6 parts/billion (ppb),l-NMMA 18 ± 4 ppb; P = 0.51]. Neither treatment had any impact on the FEV1, pulse, or blood pressure. After l-NMMA, FeNO fell significantly ( P < 0.0001), the stimulus-response curves shifted to the right, and the minute ventilation required to reduce the FEV1 20% rose 53.5% over control ( P = 0.02). The results of this study demonstrate that NO generated from the airways of asthmatic individuals may play an important role in the pathogenesis of thermally induced asthma.

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Tachykinins mediate bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.3.1108 ◽

1989 ◽

Vol 66 (3) ◽

pp. 1108-1112 ◽

Cited By ~ 34

Author(s):

D. W. Ray ◽

C. Hernandez ◽

A. R. Leff ◽

J. M. Drazen ◽

J. Solway

Keyword(s):

Tidal Volume ◽

Guinea Pigs ◽

Minute Ventilation ◽

Response Curves ◽

Mechanically Ventilated ◽

Stimulus Response ◽

Respiratory System Resistance ◽

Water Saturated ◽

And Control ◽

Isocapnic Hyperpnea

We tested the hypothesis that tachykinins mediate hyperpnea-induced bronchoconstriction (HIB) in 28 guinea pigs. Stimulus-response curves to increasing minute ventilation with dry gas were generated in animals depleted of tachykinins by capsaicin pretreatment and in animals pretreated with phosphoramidon, a neutral metalloendopeptidase inhibitor. Sixteen anesthetized guinea pigs received capsaicin (50 mg/kg sc) after aminophylline (10 mg/kg ip) and terbutaline (0.1 mg/kg sc). An additional 12 animals received saline (1 ml sc) instead of capsaicin. One week later, all animals were anesthetized, given propranolol (1 mg/kg iv), and mechanically ventilated (6 ml/kg, 60 breaths/min, 50% O2 in air fully water saturated). Phosphoramidon (0.5 mg iv) was administered to five of the noncapsaicin-treated guinea pigs. Eucapnic dry gas (95% O2–5% CO2) hyperpnea “challenges” were performed by increasing the tidal volume (2–6 ml) and frequency (150 breaths/min) for 5 min. Capsaicin-pretreated animals showed marked attenuation in HIB, with a rightward shift of the stimulus-response curve compared with controls; the estimated tidal volume required to elicit a twofold increase in respiratory system resistance (ES200) was 5.0 ml for capsaicin-pretreated animals vs. 3.7 ml for controls (P less than 0.03). Phosphoramidon-treated animals were more reactive to dry gas hyperpnea compared with control (ES200 = 2.6 ml; P less than 0.0001). Methacholine dose-response curves (10(-11) to 10(-7) mol iv) obtained at the conclusion of the experiments were similar among capsaicin, phosphoramidon, and control groups. These findings implicate tachykinin release as an important mechanism of HIB in guinea pigs.

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