Effect of gallopamil, a calcium channel blocker, on carbachol- and histamine-induced bronchoconstriction in sheep.
We compared the in vivo effectiveness of the calcium channel blockers, gallopamil and verapamil, in inhibiting carbachol- and histamine-induced bronchoconstriction in conscious sheep. In 13 sheep, specific lung resistance (SRL) was measured before and after aerosol challenge with histamine (50 breaths; 5% solution) and carbachol (10 breaths; 2.5% solution), without and with pretreatment with intravenous and aerosolized gallopamil and verapamil. Histamine increased mean SRL by 213%. Intravenous (20 micrograms/kg) and aerosolized (5 mg) gallopamil markedly inhibited the histamine-induced bronchoconstriction. Mean SRL increased by 19% and 23%, respectively, whereas 2.5 mg of aerosolized gallopamil partly inhibited the histamine-induced response with SRL increasing by 115% (p less than 0.05). Carbachol increased mean SRL by 380%. Pretreatment with 2.5 mg of aerosolized gallopamil had no effect on carbachol-induced bronchoconstriction, whereas intravenous and 5 mg of aerosolized gallopamil partly attenuated the carbachol response; mean SRL increased by 204% and 177%, respectively (p less than 0.05). Intravenous (150 micrograms/kg) and aerosolized (10 mg and 20 mg) verapamil did not prevent either histamine- or carbachol-induced bronchoconstriction. These results indicate that gallopamil (parenteral and aerosol) attenuates carbachol- and histamine-induced bronchoconstriction, is more potent than verapamil, and may be of therapeutic potential.
Carpenter
N
N
Division of Pulmonary Disease, University of Miami School of Medicine, FL 33140.
D'Brot
J
J
Kim
C S
CS
Abraham
W M
WM
Ahmed
T
T
D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001986:Bronchial Spasm / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D002217:Carbachol; D005260:Female; D005711:Gallopamil / Q000008:administration & dosage*; D006632:Histamine; D007262:Infusions, Intravenous; D012756:Sheep; D014700:Verapamil / Q000008:administration & dosage
D000336:Aerosols; D005711:Gallopamil; D006632:Histamine; D002217:Carbachol; D014700:Verapamil