Effect of cigarette smoke extract on neonatal porcine vascular smooth muscle cells.
BACKGROUND
Cigarette smoke exposure in the perinatal period increases the risk of various prenatal and postnatal complications, including sudden infant death syndrome (SIDS) and persistent pulmonary hypertension of the newborn (PPHN). We investigated the cellular effects of cigarette smoke extract (CSE) in the developing vasculature.


METHODS
Vascular smooth muscle cells (VSMC) were isolated from neonatal porcine carotid arteries, splenic arteries, and main and resistance pulmonary arteries. Effects of CSE on VSMC proliferation, viability, apoptosis, and media nitrates and nitrites were evaluated. The effects of known constituents of CSE (nicotine, benzopyrene, acrolein, acetaldehyde), aged CSE, CSE with added hemoglobin, devolatilized CSE, CSE with added dithiothreitol (DTT), and reduced glutathione (GSH) on cell proliferation and viability were assessed.


RESULTS
CSE caused a dose- and time-dependent decrease in neonatal VSMC numbers isolated from all four sites, mainly as a result of increased cell necrosis and not apoptosis. Nitrates and nitrites were below the threshold of detection. Nicotine and benzopyrene did not affect cell counts, while acrolein and acetaldehyde decreased cell counts in a dose-dependent manner. Addition of hemoglobin, devolatilization, and the addition of DTT or GSH slightly decreased CSE inhibition.


CONCLUSIONS
CSE causes necrosis of neonatal VSMC, and this toxicity is mediated mainly by volatile components such as acrolein and acetaldehyde, possibly in association with nitric oxide and carbon monoxide.
Ambalavanan
N
N
Department of Pediatrics, Division of Neonatology, University of Alabama at Birmingham, 525 New Hillman Bldg., Birmingham, AL 35233-7335, USA. ambal@sprynet.com
Carlo
W F
WF
Bulger
A
A
Shi
J
J
Philips
J B
JB
D000079:Acetaldehyde / Q000633:toxicity; D000171:Acrolein / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009538:Nicotine / Q000633:toxicity; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010947:Plants, Toxic; D012906:Smoke / Q000009:adverse effects*; D013552:Swine; D014026:Nicotiana
D003470:Culture Media; D009566:Nitrates; D009573:Nitrites; D012906:Smoke; D009538:Nicotine; D000171:Acrolein; D000079:Acetaldehyde