Abstract
Maternal smoking with obligatory nicotine inhalation is associated with preterm delivery, low birth weight, fetal growth retardation and developmental defects. We tested the hypothesis that cigarette smoking-relevant nicotine inhalation during pregnancy impairs cardiovascular function and uterine hemodynamics with consequential fetal ischemia. Pregnant rats exposed to episodic inhaled nicotine via a novel lung alveolar region-targeted aerosol method produced nicotine pharmacokinetics resembling cigarette smoking in humans. This clinically relevant nicotine aerosol inhalation (NAI) induced transient reduction and irregular fluctuations in uterine artery blood flow associated with cardiac arrhythmia and high magnitude irregular fluctuations of systemic blood pressure. The arrhythmia included sinoatrial (SA) block, sinus arrest, 2° and 3° atrioventricular (A-V) block and supraventricular escape rhythm. These effects were blocked by the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine. Resection of the ovarian nerve, which innervates uterine blood vessels, counteracted the NAI-induced reduction in uterine blood flow. We suggest that the rapid rise pattern of arterial blood nicotine concentration stimulates and then desensitizes autonomic nAChRs leading to disruptions of cardiac function as well as systemic and uterine hemodynamics that reduces uteroplacental blood flow, a mechanism underlying maternal smoking-associated pregnancy complications and developmental disorders. These findings challenge the safety of pure nicotine inhalation, i.e., E-cigarettes.
Highlights
Maternal smoking increases the risk of preterm delivery, low birth weight, fetal growth retardation, sudden infant death syndrome (SIDS) and developmental defects[1]
We tested the hypothesis that nicotine aerosol inhalation (NAI) exposure in dose and kinetics equivalent to that in human smoking stimulates autonomic nicotinic acetylcholine receptor (nAChR) resulting in disturbances in cardiac function and systemic hemodynamics as well as vasoconstriction of the uterine artery that disrupt uteroplacetal hemodynamics, which can lead to fetal ischemia
Blood flow periodicity was disturbed while the cross-correlation with cardiac activity persisted. These results suggest that NAI-induced cardiac arrhythmia and irregular cardiac output disrupted rhythmic uterine blood flow and hemodynamics
Summary
Maternal smoking increases the risk of preterm delivery, low birth weight, fetal growth retardation, sudden infant death syndrome (SIDS) and developmental defects[1]. We tested the hypothesis that NAI exposure in dose and kinetics equivalent to that in human smoking stimulates autonomic nAChRs resulting in disturbances in cardiac function and systemic hemodynamics as well as vasoconstriction of the uterine artery that disrupt uteroplacetal hemodynamics, which can lead to fetal ischemia. This provides a mechanistic link between maternal smoking and its adverse effects on pregnancy and fetal development
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