Smoking increases plasma levels of
thromboxane (Tx) B2. Since intravenous
nicotine is without effect on platelet TxB2 synthesis, it is likely that lung parenchyma is the site of metabolic importance. This study examines the TxB2 response and functional consequences to the lungs of intratracheal and intravenous instillations of
nicotine tartrate. Rat lungs perfused with Krebs-Henseleit (K-H)
solution without recirculation were used. After hemodynamic stabilization, the perfusate was either left unaltered or switched to 5 X 10(-4)
M nicotine. After 20 minutes of K-H perfusion, effluent levels of TxB2 fell from 41 +/- 6 pg/ml (mean +/- standard error) to 16 +/- 5 pg/ml. A similar decline was noted with
nicotine perfusion. K-H perfusion was used throughout the second set of experiments. The lungs were instilled with either
saline solution (1 ml/kg
body weight) or 5 X 10(-4)
M nicotine in
saline solution. In the
nicotine group, TxB2 levels rose to 86 +/- 5 pg/ml versus 22 +/- 3 pg/ml in saline-instilled controls (p less than 0.05). In addition,
pulmonary edema developed in
nicotine-instilled lungs. Pretreatment with the Tx synthase inhibitor
OKY-046 prevented the rise in TxB2 concentration after
nicotine instillation and led to a wet weight/dry weight ratio of 4.0 +/- 0.4 versus 7.5 +/- 1.5 in untreated control lungs (p less than 0.05). Pretreatment with the
lipoxygenase inhibitor diethylcarbamazine increased TxB2 levels to 235 +/- 34 pg/ml (p less than 0.05).
Diethylcarbamazine also lowered pulmonary artery pressure from 18 +/- 1 mm Hg to 6.1 +/- 0.7 mm Hg in control lungs (p less than 0.05) but did not reduce
edema formation.(ABSTRACT TRUNCATED AT 250 WORDS)