Effect of aerosolized acetylcholine on bronchial blood flow.
We studied the effects of aerosolized as well as intravenous infusion of acetylcholine on bronchial blood flow in six anesthetized sheep. Intravenous infusion of acetylcholine, at a dose of 2 microg/kg, increased bronchial blood flow from 45 +/- 15 (SE) to 74 +/- 30 ml/min, and vascular conductance increased by 76 +/- 22%. In contrast, aerosolized acetylcholine at doses of 2 and 20 microg/kg decreased bronchial vascular conductance by approximately 10%. At an aerosolized dose of 200 microg/kg, the bronchial vascular conductance increased by approximately 15%, and there was no further increase in conductance when the aerosolized dose was increased to 2,000 microg/kg. Pretreatment of animals with a nitric oxide synthase inhibitor, Nomega-nitro-L-arginine methyl ester hydrochloride, partially blocked the vasodilatory effects of intravenous acetylcholine and completely blocked the vasodilatory effects of high-dose aerosolized acetylcholine. These data suggest that aerosolized acetylcholine does not readily penetrate the vascular wall of bronchial circulatory system and, therefore, has minimal vasodilatory effects on the bronchial vasculature.
Pulmonary Research Laboratory, Veterans Affairs Medical Center, Boise, Idaho 83702, USA. ncharan@u.washington.edu
N B
NB
Charan
P
P
Carvalho
S R
SR
Johnson
W H
WH
Thompson
S
S
Lakshminarayan
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000336:Aerosols; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000098:blood supply* / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007262:Infusions, Intravenous; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011652:Pulmonary Circulation / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D013990:Tidal Volume / Q000187:drug effects; D018924:Vascular Capacitance / Q000187:drug effects
D000336:Aerosols; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester