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

Hypertension Research volume 43, pages 178–185 (2020)Cite this article

Abstract

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.

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Acknowledgements

This study was supported in part by the Smoking Research Foundation and by the Grants-in-Aid for Scientific Research Program from the Japan Society for the Promotion of Science (grant no. 17K15579).

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Authors and Affiliations

  1. Department of Pharmacology, Kanazawa Medical University, Kahoku, Ishikawa, Japan

    Masashi Tawa, Takayoshi Masuoka, Yuka Yamashita, Katsuya Nakano, Matomo Nishio & Takaharu Ishibashi

  2. Division of Cardiovascular Surgery, Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan

    Takeshi Kinoshita

  3. Department of Pharmacology, Shiga University of Medical Science, Otsu, Shiga, Japan

    Tomio Okamura

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  1. Masashi Tawa
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Correspondence to Masashi Tawa.

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Tawa, M., Kinoshita, T., Masuoka, T. et al. Impact of cigarette smoking on nitric oxide-sensitive and nitric oxide-insensitive soluble guanylate cyclase-mediated vascular tone regulation. Hypertens Res 43, 178–185 (2020). https://doi.org/10.1038/s41440-019-0363-y

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