Activation of platelets exposed to shear stress in the presence of smoke extracts of low-nicotine and zero-nicotine cigarettes: The protective effect of nicotine

Mainstream and sidestream smoke extracts of both high-tar and low-tar cigarettes have been shown to increase platelet activation directly and to sensitize them to further activation by exposure to mechanical stimuli such as shear stress. However, nicotine has an inhibitory effect on platelet activation, opposite to that of whole cigarette smoke extracts. To distinguish between the nicotine-dependent and non-nicotine-dependent effects of smoke, platelets were exposed to mainstream and sidestream smoke extracts of low-nicotine and zero-nicotine cigarettes in vitro under flow conditions comparable with the normal circulation, and their activation state was measured using a modified prothrombinase-based assay. Both low-nicotine and zero-nicotine extracts caused increased platelet activation upon exposure to shear stress, and they caused significantly greater activation than extracts from ordinary high-tar, high-nicotine cigarettes. That nicotine was crucial was confirmed by adding 50 nM nicotine (comparable with the nicotine level in smokers' plasma) to zero-nicotine smoke extracts and demonstrating a reduction in the shear-dependent rate of platelet activation of more than 75%.