Effects of prenatal nicotine exposure on vascular endothelial function and structure in offspring rats

Abstract

To clarify the effect of prenatal nicotine exposure (PNE) on vascular endothelial function (VEF) in offspring rats, and to explore whether these effects are long-lasting and sex-dependent. Pregnant Sprague-Dawley rats were randomized into two groups and exposed to either 102 mg/mL nicotine (experimental group) or normal saline (control group) through a subcutaneously implanted osmotic micropump. Vascular rings from the thoracic aorta were collected from offspring rats at 1, 4, and 12 months of age. The specimens were used to determine VEF using functional tests and to observe morphologic and pathologic changes of blood vessels in hematoxylin and eosin-stained samples with light microscopy. The percentage of acetylcholine-induced endothelium-dependent vasorelaxation (EDV) of the thoracic aorta was significantly higher in the experimental group than in the control group in 1-, 4-, and 12-month-old female offspring rats (18.68±2.32 vs. 13.85±6.10, 17.44±3.91 vs. 10.77±5.77, and 30.96±22.26 vs. 18.94±13.61, respectively; P <0.05). The percentage of acetylcholine-induced EDV was significantly lower in the experimental group than in the control group in 1-, 4-, and 12-month-old male offspring rats (10.31±4.05 vs. 16.05±14.80, 5.57±2.81 vs. 12.12±5.62, and 11.98±7.24 vs. 58.87±32.43, respectively; P <0.05). The hematoxylin & eosin-stained vascular rings of the offspring rats displayed an uneven lumen, scattered intimal thickening, partial shedding and vacuolar degeneration of endothelial cells, and inflammatory cell infiltration and phagocytosis in the experimental group. In addition, overt smooth muscle atrophy in tunica media, disordered cell arrangement, and unclear structure of the elastic fiber layer was observed. None of these histopathologic changes were found in the control group. In adult offspring rats, PNE not only affected the VEF of the thoracic aorta but also led to pathologic changes in the vascular structure. Additionally, the effects of PNE on VEF were sex-specific, manifesting primarily as significantly improved VEF in female offspring rats and significantly impaired VEF in male offspring rats, lasting into adulthood.