Nicotine stimulates pulmonary parenchymal thromboxane synthesis.
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)
D000818:Animals; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000139:chemically induced; D051381:Rats; D013268:Stimulation, Chemical; D013929:Thromboxane B2 / Q000096:biosynthesis*
D013929:Thromboxane B2; D009538:Nicotine