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36: Effects of fetal nicotine exposure on developmental programming of adult blood pressure and vascular reactivity

      Objective

      Smoking has been linked to adverse pregnancy outcomes relating to utero-placental insufficiency. We hypothesized that fetuses exposed to nicotine would also have long term consequences relating to developmental programming of cardiovascular function. The aim of this study was to assess long-term cardiovascular effects in offspring exposed to nicotine during development.

      Study Design

      C57Bl/CJ female mice were randomized to drinking water alone or 200mcg/ml nicotine in water starting 2 weeks prior to breeding. Maternal cotinine levels were measured at baseline, prior to breeding and at weaning. When they reached 5 months of age, blood pressure was continuously monitored for 6 days in the unrestrained offsprings by telemetry. They were then sacrificed, and their carotid arteries were isolated for in vitro vascular reactivity studies. One-way ANOVA, Kruksal-Wallis, Student-t and post hoc multiple comparison tests were used for statistical analysis as appropriate (significance: P<0.05).

      Results

      Cotinine levels were minimal in all mice prior to breeding (1.54 +/− 0.05 test group; 0.78 +/− 0.45 mcg/ml control, P>0.05). At weaning, maternal cotinine levels were higher in the nicotine group compared to controls (100.0 +/− 9.6 vs 1.49 +/− 0.08 mcg/ml, P=0.009). Fetal nicotine exposure increased median systolic and diastolic blood pressure by 8.7-10.6 mmHg and 11.35-13.1 mmHg respectively in female, but not male, offspring (P<0.001, Fig. 1) . Offspring exposed to nicotine exhibited strikingly blunted vascular contractility in response to phenylephrine (Fig. 2), which was mitigated in the presence of L-NAME, a nitric oxide synthase inhibitor. This effect was more pronounced in male versus female offspring.

      Conclusion

      Nicotine exposure during development produces gender-specific effects on blood pressure and vascular function in adult offspring. This effect appears to be partly endothelial-dependent. We speculate that nicotine alters fetal nicotinic receptor subtype number and activity in the vasculature, in addition to neural pathways contributing to central blood pressure regulation.