Impact of cigarette smoking on nitric oxide-sensitive and nitric oxide-insensitive soluble guanylate cyclase-mediated vascular tone regulation

• Published in: Hypertension research 2020-03, Vol.43 (3), p.178-185
• Main Authors: Tawa, Masashi, Kinoshita, Takeshi, Masuoka, Takayoshi, Yamashita, Yuka, Nakano, Katsuya, Nishio, Matomo, Okamura, Tomio, Ishibashi, Takaharu
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Adult; Animals; Aorta - drug effects; Cigarette Smoking - physiopathology; Cigarettes; Female; Gastroepiploic Artery - drug effects; Gastroepiploic Artery - physiopathology; Humans; Hypertension; Male; Middle Aged; Nitric oxide; Nitric Oxide - physiology; Nitric Oxide Donors - pharmacology; Nitroprusside - pharmacology; Pulmonary arteries; Pulmonary Artery - drug effects; Pulmonary Artery - physiopathology; Rats; Reactive Oxygen Species - blood; Smoking; Soluble Guanylyl Cyclase - physiology; Thiobarbituric Acid Reactive Substances - metabolism; Vasodilation - drug effects; Vasodilation - physiology; Veins & arteries; Young Adult
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1038/s41440-019-0363-y

Cigarette smoking induces vascular endothelial dysfunction characterized by impaired nitric oxide (NO) bioavailability. There are two types of soluble guanylate cyclase (sGC), which is a cellular target of NO: NO-sensitive reduced form (the heme moiety with a ferrous iron) and NO-insensitive oxidized (the heme moiety with a ferric iron)/heme-free form. This study investigated the influence of cigarette smoking on NO-sensitive and NO-insensitive sGC-mediated vascular tone regulation in organ chamber experiments with isolated rat and human arteries. The rats were subcutaneously administered phosphate-buffered saline (PBS), nicotine-free cigarette smoke extract (N(-)-CSE) or nicotine-containing cigarette smoke extract (N(+)-CSE) for 4 weeks. Plasma thiobarbituric acid reactive substance (TBARS) levels were higher in the N(+)-CSE group than those in the N(-)-CSE group, and TBARS levels for these groups were higher than those for the PBS group. In the aorta and the pulmonary artery in rats administered N(-)-CSE or N(+)-CSE, acetylcholine-induced relaxation was significantly impaired compared with that in rats administered PBS; there was no significant difference in the relaxation between the N(-)-CSE and N(+)-CSE groups. However, sodium nitroprusside (NO-sensitive sGC stimulant)- and BAY 60-2770 (NO-insensitive sGC stimulant)-induced relaxations were not different among the three groups, regardless of the vessel type. In addition, in the human gastroepiploic artery, the relaxant responses to these sGC-targeting drugs were identical between nonsmokers and smokers. These findings suggest that NO-sensitive and NO-insensitive sGC-mediated vascular tone regulation functions normally even in blood vessels damaged by cigarette smoking.