Electronic cigarette vape decreases nitric oxide bioavailability in vascular smooth muscle cells via increased...

Cytoglobin (Cygb) regulates vascular tone by modulating nitric oxide (NO) metabolism in vascular smooth muscle cells (VSMCs). In the presence of its cytochrome B5a (B5)/B5 reductase-isoform-3 (B5R) reducing system, Cygb controls NO metabolism via oxygen-dependent NO dioxygenation. Electronic cigarette (EC) use has been shown to induce vascular dysfunction and decrease NO bioavailability; however, the role of Cygb-mediated NO metabolism in the pathophysiology of this process has not been previously investigated. Therefore, we utilized aortic VSMCs with EC vape extract (ECE) exposure to elucidate the effects of EC vape constituents on NO degradation and alterations in the process of Cygb-mediated NO metabolism. VSMCs were exposed to ECE, either nicotine-free (ECEV) or nicotine-containing (ECEN), for various durations. NO decay rates were measured along with cellular expression of Cygb and its B5/B5R reducing system. Exposure to ECEV led to a much higher rate of NO consumption by VSMCs, with an even larger effect following ECEN exposure. With 4 h of exposure, a modest increase in NO decay rate occurred that was followed by much higher increases with exposure times of 24-48 h. This effect was paralleled by upregulation of Cygb and B5/B5R expression. siRNA-mediated knock-down of Cygb expression largely reversed this ECE-induced increase in NO metabolism rate. Thus, ECE exposure led to increased Cygb-mediated NO metabolism in VSMCs with diminished NO bioavailability, which in turn can play a key role in EC-induced vascular dysfunction.