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Sex Dependent Effects of Prenatal Nicotine Exposure on Cardiovascular Reactivity: Are Males at a Greater Risk for Cardiovascular Disease?
Author(s) -
Hayward Linda F,
Watkins Jacqueline
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.850.6
Subject(s) - nicotine , offspring , medicine , endocrinology , pregnancy , prenatal stress , biology , genetics
Prenatal nicotine exposure (PNE) has been linked to an increased incidence of anxiety‐disorders, risk of nicotine use, and dysregulation of the hypothalamic orexin system. Recent data link dysregulation of the orexin system to cardiovascular disease. The aim of this study was to evaluate cardiovascular reactivity of adult offspring exposed to nicotine in utero and correlate differences with changes in orexin system gene expression in the hypothalamus and amygdala. Pregnant Sprague Dawley rats had an osmotic mini‐pump filled with nicotine implanted on day 6 of pregnancy (exposure dose 3 mg/kg). At 12 weeks of age (n=4–6/group) offspring were instrumented with arterial catheters and tested 2 days later. PNE male and female weighed ~20% more than controls (P<0.05) but resting mean arterial pressure (MAP) was not significantly different between groups. After an acute dose of nicotine (0.37mg/kg), MAP increased ~ 9 mm Hg in females and 6 mm Hg in male within 2 min. of a subcutaneous (sc) injection, independent of prenatal treatment At 18 minutes' post nicotine injection, MAP in both male and female controls and PNE females decreased significantly below baseline (−9 mmHg) while the MAP of PNE males returned to baseline. There was a strong trend (P<0.07) for the pressor response to angiotensin II (10 microg/kg) to be greater in the PNE males compared to control but not for the PNE females when compared to sex‐matched controls. In the hypothalamus orexin‐type 1 receptor gene expression was increased significantly in PNE males compared to controls (P<0.006). Alternatively, in the amygdala a decrease in orexin‐type 2 receptors in PNE females compared to controls (P<0.03) was identified These results suggest that male offspring exposed to nicotine in utero may be more susceptible to the negative cardiovascular consequences of nicotine when compared to females due to sex‐dependent changes in orexin‐receptor gene expression in the brain. Support or Funding Information Florida Department of Health‐James and Esther King Biomedical Research Program