Cigarette smoke extracts inhibit prostacyclin synthesis by the rat urinary bladder

Since prostacyclin (PGI₂) is known to have a cytoprotective effect on epithelia, and since cigarette smoking is associated with an increased risk of bladder cancer, we investigated the possibility that nicotine, cotinine (the prinicpal metabolite of nicotine) and other components of cigarette smoke inhibit PGI₂ secretion by the urinary bladder. Using the rat urinary bladder as a model, we found that cigarette smoke extracts, but not nicotine or cotinine, inhibit in vitro PGI₂ synthesis. 2-Naphthylamine, a known bladder carcinogen, was also a potent inhibitor of PGI₂ synthesis by the rat bladder. It is possible that cigarette smoke and 2-napthylamine exert their carcinogenic effect partly through the inhibition of PGI₂ synthesis, resulting in diminished urothelial cytoprotection.