Effect of prenatal nicotine exposure on coronary flow in adult offspring: a gender dichotomy

Abstract

Maternal cigarette smoking is the single most widespread prenatal insult. Smoking has long been associated with adverse pregnancy outcomes, both for the mother, her fetus, and newborn. The present study was designed to test the hypothesis that fetal and neonatal nicotine exposure has adverse effects on coronary vasculature development, resulting in changes in coronary blood flow in adult offspring. Nicotine (2.1mg/d) was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation and up to 10 days after delivery. Hearts were isolated from 3 month-old male and female offspring, and were subjected to 25-min of ischemia followed by 60-min of reperfusion in a Langendorff preparation. Pulmonary artery effluent was collected as an index of coronary flow (ml/min/g heart wet weight). Nicotine significantly decreased coronary flow in female (10.4±0.8 vs. 7.1±0.7, P<0.05) but not in male (9.1±0.5 vs. 9.0±0.7, P>0.05) hearts at baseline. Ischemia and reperfusion decreased coronary flow in both male and female hearts, with higher coronary flow in female hearts. Nicotine treatment significantly decreased coronary flow during reperfusion up to 60 min in female, but not in male, hearts. The results suggest that prenatal nicotine exposure selectively decreases coronary flow in adult female offspring. (Supported in part by NIH grant S06GM073842 and TRDRP Award # 14FT-0075)