TY - JOUR
T1 - Lemakalim attenuates hypocapnia- and dry air-induced bronchoconstriction in canine peripheral airways
AU - Lindeman, K. S.
AU - Freed, A. N.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1993
Y1 - 1993
N2 - To determine the effect of changes in potassium (K+) flux on airway constriction, we studied effects of lemakalim, a K+ channel opener, and glibenclamide, an ATP-sensitive K+ channel blocker. A wedged bronchoscope technique was used to measure peripheral airway resistance (Rp) in anesthetized dogs. Rp was measured before and after constriction of the airways by hypocapnic challenge, acetylcholine aerosol, or dry air hyperpnea. Lemakalim (5 μg/kg iv) was administered, and the challenge was repeated. Lemakalim attenuated responses to hypocapnia by 72 ± 7% (n = 6, P = 0.0007) and to dry air challenge by 37 ± 8% (n = 6, P = 0.005) but not to acetylcholine. On separate days, sublobar segments were pretreated with aerosolized glibenclamide (2 mg/ml), and responses to hypocapnic challenge were measured before and after lemakalim (5 μg/kg iv), nifedipine (20 μg/kg iv), or albuterol (1 μg/kg iv). In the presence of glibenclamide, lemakalim had no significant effect on responses to hypocapnia; however, both nifedipine (n = 6, P = 0.0003) and albuterol (n = 6, P = 0.0001) attenuated responses to hypocapnic challenge. These findings suggest that lemakalim attenuated hypocapnic bronchoconstriction by promoting K+ efflux through ATP-sensitive K+ channels.
AB - To determine the effect of changes in potassium (K+) flux on airway constriction, we studied effects of lemakalim, a K+ channel opener, and glibenclamide, an ATP-sensitive K+ channel blocker. A wedged bronchoscope technique was used to measure peripheral airway resistance (Rp) in anesthetized dogs. Rp was measured before and after constriction of the airways by hypocapnic challenge, acetylcholine aerosol, or dry air hyperpnea. Lemakalim (5 μg/kg iv) was administered, and the challenge was repeated. Lemakalim attenuated responses to hypocapnia by 72 ± 7% (n = 6, P = 0.0007) and to dry air challenge by 37 ± 8% (n = 6, P = 0.005) but not to acetylcholine. On separate days, sublobar segments were pretreated with aerosolized glibenclamide (2 mg/ml), and responses to hypocapnic challenge were measured before and after lemakalim (5 μg/kg iv), nifedipine (20 μg/kg iv), or albuterol (1 μg/kg iv). In the presence of glibenclamide, lemakalim had no significant effect on responses to hypocapnia; however, both nifedipine (n = 6, P = 0.0003) and albuterol (n = 6, P = 0.0001) attenuated responses to hypocapnic challenge. These findings suggest that lemakalim attenuated hypocapnic bronchoconstriction by promoting K+ efflux through ATP-sensitive K+ channels.
KW - albuterol
KW - calcium channels
KW - collateral resistance
KW - nifedipine
KW - potassium channels
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U2 - 10.1152/jappl.1993.75.1.86
DO - 10.1152/jappl.1993.75.1.86
M3 - Article
C2 - 8376305
AN - SCOPUS:0027295784
SN - 8750-7587
VL - 75
SP - 86
EP - 92
JO - Journal of applied physiology
JF - Journal of applied physiology
IS - 1
ER -