Influence of nicotine on basal and stimulated prostaglandin biosynthesis in perfused vascular tissue of the rabbit.

Abstract

1. The prelabelling technique [incorporation of (1-14C)-arachidonic acid] was used to investigate the influence of nicotine (in comparison with acetylcholine) on release and metabolism of arachidonic acid in the isolated perfused rabbit ear. 2. Injection of increasing amounts of nicotine (up to 300 μg) intra-arterially into the isolated rabbit ear did not influence the small basal release of prostaglandins or arachidonic acid. Injection of acetylcholine or bethanechol dosedependently stimulated the release of prostacyclin. Bethanechol stimulated the release of prostaglandin E2, too. The release of arachidonic acid was not significantly increased by injections of acetylcholine or bethanechol. 3. The release of prostaglandins by bethanechol or acetylcholine was abolished by atropine (5 μg/ml) but remained unaffected by hexamethonium (10 μ/ml). 4. Nicotine (10 μg/ml) strongly reduced a histamine-stimulated release of prostaglandins I2 and E2. Acetylcholine (10 μg/ml) also reduced the histamine-evoked release of prostaglandins but to lesser extent. 5. Labelled arachidonic acid, infused through the ear was incorporated at 75.8%. The rest was immediately converted to a small part into prostaglandins. This conversion into PGI2 and PGE2 was reduced by nicotine (10 μg/ml) but not by acetylcholine (10 μg/ml). 6. Infusion of nicotine (10 μg/ml) did not significantly influence the basal release of prostaglandins. Infusion of acetylcholine (10 μg/ml) led to an immediate increase in the release of prostacyclin and — to a somewhat lower amount —of PGE2. The increase underwent tachyphylaxis and was abolished after 30 min of infusion. The basal release of arachidonic acid was initially increased by infusion of acetylcholine and became lower than the initial basal levels after 30 min of infusion. No other substance significantly in-fluenced the release of arachidonic acid. 7. The results show that acetylcholine first stimulates the release of prostacyclin from peripheral vessels via muscarinic receptors and then reduces the stimulated release of prostaglandins possibly due to tachyphylaxis. Nicotine strongly reduces the stimulated release of prostacyclin and PGE2 possibly due to inhibition of the cyclo-oxygenase. A further influence on the following enzymes, e. g. on prostacyclin synthetase cannot be excluded. A reduced generation of prostacyclin by nicotine may lead to a reduced protection of the endothelium and to an increased tendency of platelet aggregation especially in predamaged vessels.