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BMC Pharmacology and Toxicology

Open Access

Influence of smoking on vascular reactivity to cGMP generators in human internal thoracic arteries

  • Masashi Tawa1Email author,
  • Takeshi Kinoshita2,
  • Tohru Asai2,
  • Tomoaki Suzuki2,
  • Takeshi Imamura1 and
  • Tomio Okamura1
BMC Pharmacology and Toxicology201516(Suppl 1):A93

https://doi.org/10.1186/2050-6511-16-S1-A93

Published: 2 September 2015

Background

There are nitric oxide (NO)-sensitive and -insensitive forms of soluble guanylyl cyclase (sGC). This balance is shifted to the latter under stress conditions associated with increased production of reactive oxygen species (ROS) [1, 2]. The present study investigated whether smoking, a well-documented source of ROS, affects NO-sensitive and -insensitive sGC-mediated effects in human arteries.

Materials and methods

Mechanical responses of internal thoracic arteries obtained from 29 patients undergoing coronary artery bypass grafting were studied. The patients were divided into 2 groups according to their smoking habits: current or ever-smokers (n=17) and former or never-smokers (n=12). Concentration-response curves for nitroglycerin and BAY 60-2770 were constructed in helically-cut strips pre-contracted with phenylephrine, and the values of potency (pD2) were calculated. Relaxations induced by the agonists were presented as relative values to the relaxation caused by 10-4 M papaverine. Concentration-response curves were analyzed using two-way repeated measures analysis of variance and Bonferroni post hoc test. pD2 values were compared with unpaired two-tailed Student's t-test.

Results

The mean ages of smokers and non-smokers were 70.3 ± 2.1 and 72.3 ± 2.1 years, respectively. The portion of men in smokers (88.2%) was notably higher than that in non-smokers (41.7%). Clinical conditions, laboratory parameters, and medications were similar between the two populations. As shown in Figure 1A, nitroglycerin caused a dose-dependent relaxation, which was not different in the arteries from smokers and non-smokers. pD2 values were also identical: 8.03 ± 0.14 (non-smokers) vs. 7.81 ± 0.11 (smokers), p=0.23. Similarly, there was no significant difference in the relaxant potency (pD2 values, 9.43 ± 0.22 and 9.15 ± 0.14 for non-smokers and smokers, respectively, p=0.26) and efficacy of BAY 60-2770 (Figure 1B).
Figure 1

Vasorelaxation induced by nitroglycerin (A) or BAY 60-2770 (B) in internal thoracic arteries from non-smokers (white circle) and smokers (black circle). Each point and bar represents the mean ± SEM of 12 (non-smokers) or 17 (smokers) experiments.

Conclusion

It was demonstrated that smoking is not causal factor for the imbalance between NO-sensitive and -insensitive forms of sGC in human internal thoracic arteries.

Authors’ Affiliations

(1)
Department of Pharmacology, Shiga University of Medical Science
(2)
Division of Cardiovascular Surgery, Department of Surgery, Shiga University of Medical Science

References

  1. Tawa M, Shimosato T, Iwasaki H, Imamura T, Okamura T: Effects of peroxynitrite on relaxation through the NO/sGC/cGMP pathway in isolated rat iliac arteries. J Vasc Res. 2014, 51 (6): 439-446. 10.1159/000371491.View ArticlePubMedGoogle Scholar
  2. Tawa M, Shimosato T, Iwasaki H, Imamura T, Okamura T: Different influences of extracellular and intracellular superoxide on relaxation through the NO/sGC/cGMP pathway in isolated rat iliac arteries. J Cardiovasc Pharmacol. 2015, 65 (2): 160-167.PubMedGoogle Scholar

Copyright

© Tawa et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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