Discussion
fibrin-rich thrombus, platelet thrombus, platelet aggregation
VASODILATION, OXIDATIVE STRESS, VASODILATATION
We investigated the effects of brief EC inhalation with and without nicotine on platelet function and coagulation and microvascular function in healthy individuals. We demonstrate that exposure to EC aerosol containing nicotine was associated with increased thrombogenicity in terms of increased platelet thrombus formation and fibrin-rich thrombus formation in whole blood under flow conditions. Both the nicotine and non-nicotine EC aerosol exposures were associated with altered skin perfusion, displayed by reduced forearm and digit skin temperatures. Furthermore, inhalation of EC aerosol with nicotine had an acute impact on macro- and microvasculature in terms of increased heart rate, elevated systolic blood pressure and reduced endothelial-independent (SNP-mediated) vasodilation.Baseline T-TAS data for subjects prior to exposure correlated to other studies employing healthy controls at a similar age range [The present result of increased platelet thrombus formation following EC nicotine exposure is in line with the previous studies that have demonstrated increased platelet aggregation, heightened levels of extracellular vesicles of platelet origin and increased amounts of P-selectin in blood following EC use with nicotine in healthy individuals [A potential mechanism for EC aerosol with nicotine to induce the effects demonstrated is through the release of catecholamines that activate platelets and the sympathetic nervous system. A brief catecholamine surge caused by EC nicotine use may explain the temporary increase in thrombogenicity, increased heart rate, blood pressure and reduced skin temperature [There are several other constituents in the EC aerosol besides nicotine that have previously been suggested to affect thrombogenesis, including volatile organic compounds, ethanol and ultrafine particles [Following EC exposure with nicotine, heart rate increased significantly and systolic blood pressure showed trend of increasing compared with EC exposure without nicotine. This effect is possibly mediated by nicotine, inducing the release of neurotransmitters such as norepinephrine activating the sympathetic nervous system [No significant difference was detected between the two exposures when evaluating either endothelial-independent microcirculation (SNP-mediated response) or endothelial-dependent (ACh-mediated) microvascular response. However, nicotine containing EC exposure led to a significantly decreased SNP-mediated microvascular reactivity compared with baseline values, indicating reduced vasodilation capacity by the smooth muscle cells. SNP is a pro-drug that releases nitric oxide (NO), which is a potent vasodilating compound that diffuses into the vascular smooth muscle cells where it activates soluble guanylyl cyclase and causes vasorelaxation through formation of cyclic guanosine monophosphate (cGMP). ACh, on the other hand, exerts its effect on the vascular endothelial cells and stimulates these cells to release various vasodilating compounds including NO, prostanoids and endothelial-derived hyperpolarising factors which in turn act on the smooth muscle cell and cause them to relax. A reduction in mainly SNP-mediated vasodilatation could be explained by reduced NO bioavailability, as nicotine exposure is associated with increased oxidative stress and reactive oxygen species and free radicals react with NO [