Sources of Funding: This work was supported by the California Tobacco-related Disease Research Program Award #18KT-0024 (D. X.), and by National Institutes of Health Grants HL83966 (L. Z.), HL82779 (L. Z.), HL89012 (L. Z.) and DA025319 (S. Y.).
Antenatal nicotine induces heightened oxidative stress and vascular dysfunction in rat offspring
Article first published online: 11 OCT 2011
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society
British Journal of Pharmacology
Volume 164, Issue 5, pages 1400–1409, November 2011
How to Cite
Xiao, D., Huang, X., Yang, S. and Zhang, L. (2011), Antenatal nicotine induces heightened oxidative stress and vascular dysfunction in rat offspring. British Journal of Pharmacology, 164: 1400–1409. doi: 10.1111/j.1476-5381.2011.01437.x
- Issue published online: 11 OCT 2011
- Article first published online: 11 OCT 2011
- Accepted manuscript online: 21 JUL 2011 01:26AM EST
- Received; 21 January 2011; Revised; 8 March 2011; Accepted; 24 March 2011
- angiotensin II;
- NADPH oxidase;
- reactive oxygen species;
BACKGROUND AND PURPOSE Antenatal nicotine exposure causes aberrant vascular reactivity and increased blood pressure in adult male rat offspring in a sex-dependent manner. The present study tested the hypothesis that maternal nicotine administration increases the production of reactive oxygen species resulting in the vascular hypertensive reactivity in male offspring.
EXPERIMENTAL APPROACH Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout the gestation. The vascular oxidative damage and dysfunction were determined in 5-month-old male offspring. Contraction studies were performed on isolated aortas and their expression of NADPH oxidase (Nox2)/gp91 and nox4 determined by Western blot analysis. In addition, oxidative damage in the vessel wall was determined by measuring malondialdehyde concentrations, vascular superoxide production and SOD activity.
KEY RESULTS Antenatal nicotine significantly increased angiotensin II-induced arterial contractions in the offspring. The exaggerated vascular contractions were inhibited by both apocynin (a Nox inhibitor) and tempol (a SOD mimetic) in a concentration-dependent manner. In addition, ACh-induced relaxations were impaired in aortas isolated from the nicotine-treated offspring, which were restored by both apocynin and tempol in a concentration-dependent manner. The nicotine treatment significantly decreased the superoxide dismutase activity and increased malondialdehyde, superoxide and nitrotyrosine protein levels in the vascular wall. Consistently, antenatal nicotine exposure significantly enhanced the protein expression of NADPH oxidase Nox2/gp91, but not Nox4 in the aorta.
CONCLUSIONS AND IMPLICATIONS The present findings suggest that antenatal nicotine exposure results in the programming of heightened oxidative stress and vascular hypertensive reactivity via a Nox2-dependent mechanism, leading to an increased risk of hypertension in adult offspring.
LINKED ARTICLE This article is commented on by Lim and Sobey, pp. 1397–1399 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01488.x