Effects of flavoring compounds used in electronic cigarette refill liquids on endothelial and vascular function


Autoři: Gerald Wölkart aff001;  Alexander Kollau aff001;  Heike Stessel aff001;  Michael Russwurm aff002;  Doris Koesling aff002;  Astrid Schrammel aff001;  Kurt Schmidt aff001;  Bernd Mayer aff001
Působiště autorů: Department of Pharmacology and Toxicology, Institute of Pharmaceutical Sciences, Karl-Franzens-Universität Graz, Graz, Austria aff001;  Department of Pharmacology and Toxicology, Ruhr-Universität Bochum, Bochum, Germany aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222152

Souhrn

Electronic cigarette refill liquids are commercially provided with a wide variety of flavoring agents. A recent study suggested that several common flavors may scavenge nitric oxide (NO) and cause endothelial dysfunction. It was the aim of the present study to investigate the effects of these flavors on NO/cyclic GMP-mediated signaling and vascular relaxation. We tested the flavoring agents for effects on Ca2+-induced cGMP accumulation and NO synthase activation in cultured endothelial cells. NO scavenging was studied with NO-activated soluble guanylate cyclase and as NO release from a NO donor, measured with a NO electrode. Blood vessel function was studied with precontracted rat aortic rings in the absence and presence of acetylcholine or a NO donor. Cinnamaldehyde inhibited Ca2+-stimulated endothelial cGMP accumulation and NO synthase activation at ≥0.3 mM. Cinnamaldehyde and diacetyl inhibited NO-activated soluble guanylate cyclase with IC50 values of 0.56 (0.54–0.58) and 0.29 (0.24–0.36) mM, respectively, and caused moderate NO scavenging at 1 mM that was not mediated by superoxide anions. The other compounds did not scavenge NO at 1 mM. None of the flavorings interfered with acetylcholine-induced vascular relaxation, but they caused relaxation of pre-contracted aortas. The most potent compounds were eugenol and cinnamaldehyde with EC50 values of ~0.5 mM. Since the flavors did not affect endothelium-dependent vascular relaxation, NO scavenging by cinnamaldehyde and diacetyl does not result in impaired blood vessel function. Although not studied in vivo, the low potency of the compounds renders it unlikely that the observed effects are relevant to humans inhaling flavored vapor from electronic cigarettes.

Klíčová slova:

Biology and life sciences – Biochemistry – Neurochemistry – Neurochemicals – Nitric oxide – Neurotransmitters – Acetylcholine – Neuroscience – Psychology – Addiction – Nicotine addiction – Electronic cigarettes – Behavior – Habits – Smoking habits – Cell biology – Cellular types – Animal cells – Epithelial cells – Endothelial cells – Anatomy – Biological tissue – Epithelium – Body fluids – Blood – Plasma volume – Physiology – Social sciences – Medicine and health sciences – Mental health and psychiatry – Substance-related disorders – Smoking related disorders – Public and occupational health – Cardiovascular anatomy – Blood vessels – Pulmonology


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