Maternal smoking may increase the risk for various adverse neonatal outcomes including persistent pulmonary hypertension of the newborn (PPHN). We investigated whether chronic prenatal cigarette smoke extract (CSE) exposure could produce abnormal vasoreactivity in pulmonary arteries. Daily injections of CSE (diluted in phosphate buffered saline) or vehicle were added to the air cells of fertilized eggs starting on day 5 of the 21-day incubation period of the chicken embryo. On day 19, pulmonary arteries were dissected out and their contractile properties were assessed using small vessel myography. Endothelium-dependent and endothelium-independent vasorelaxations were examined by using acetylcholine (ACh, 10(-8) to 10(-4) M) and sodium nitroprusside (SNP, 10(-8) to 10(-4) M), respectively. The drug concentration inducing 50% of the maximal relaxation was determined for each concentration-response curve and expressed as negative log molar (pD(2)). Exposure to CSE significantly decreased the sensitivity of pulmonary arteries to ACh (pD(2) control group: 7.29 +/- 0.24; pD(2) CSE-exposed group 6.24 +/- 0.12, p < 0.05). SNP elicited similar responses in vessels of both groups at all tested concentrations. In conclusion, chronic prenatal exposure to CSE impaired endothelium-dependent but not endothelium-independent vasodilation in chicken embryo pulmonary arteries. This observation suggests that cigarette smoke components may produce deleterious effects on fetal vascular endothelial vasorelaxant pathways, leading to the development of adverse outcomes such as PPHN.