Cholinergic receptors in heart and brainstem of rats exposed to nicotine during development: implications for hypoxia tolerance and perinatal mortality
Abstract
Cigarette smoking during pregnancy increases the incidence of perinatal mortality and Sudden Infant Death Syndrome (SIDS). We have evaluated prenatal or postnatal nicotine exposure in developing rats to examine the potential role of altered neurotransmitter receptor expression in these processes. Pregnant rats received continuous infusions of nicotine throughout gestation, at doses mimicking the plasma levels found in smokers. After birth, cardiac M2-muscarinic cholinergic receptors, which are responsible for inhibitory autonomic actions, were enhanced in the nicotine group, coincidentally with decreases in stimulatory beta-adrenergic receptors that have been demonstrated previously. Studies of adenylyl cyclase activity confirmed that the changes in receptor binding represented functional alterations: the stimulatory response to isoproterenol was obtunded by prenatal nicotine exposure, whereas the inhibitory response to carbachol was enhanced. Elevations of M2-muscarinic receptor binding were not generalized to all tissues, as the same prenatal nicotine treatment elicited a reduction in these receptors in the brainstem, an effect that has also been noted in infants who died of SIDS; we found no effects of prenatal nicotine on brainstem M1-receptor binding. Postnatal administration of nicotine produced similar brainstem receptor effects when treatment was conducted during the first postnatal week but not thereafter; postnatal nicotine treatment did not affect cardiac M2-receptor binding. Thus, during a critical developmental period, nicotine exposure produces cardiac and brainstem receptor imbalances that favor inhibitory responses, effects that can contribute to morbidity and mortality evoked by hypoxic episodes, such as those experienced during parturition, sleep apnea or airway obstruction.
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Loss of cardiovascular adaptation from maternal smoking affects the fetus during delivery and infancy, when hypoxia can cause stillbirth, birth asphyxia, or SIDS.
“The loss of cardiovascular adaptation caused by maternal smoking affects the fetus during delivery, when hypoxic events can evoke stillbirth or birth asphyxia, as well as during infancy, when hypoxic events can result in SIDS.”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [107]
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- Authors
- Slotkin, T. A., Epps, T. A., Stenger, M. L., Sawyer, K. J., & Seidler, F. J.
- Affiliations
- Duke Medical Center (US)
- Corresponding author
- Slotkin, Theodore A
- ORCID
- Slotkin, Theodore A
- Venue
- Developmental Brain Research
- Publisher
- Elsevier BV
- Published
- 1999-03
- Volume
- 113
- Issue
- 1-2
- Pages
- 1-12
- ISSN
- 0165-3806 (ISSN-L)
- OpenAlex
- W1967583846
- Cited by
- 120
- References
- 5
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 1 · 2012: 4
- FWCI
- 14.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Developmental Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hd009713-25)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 09713)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- prenatal nicotine exposure, M2 muscarinic receptor, M1 muscarinic receptor, beta-adrenergic receptors, adenylate cyclase activity, brainstem, heart, hypoxia tolerance, perinatal mortality, sudden infant death syndrome, cigarette smoking during pregnancy, receptor binding, carbachol, isoproterenol
- MeSH terms
- Adenylyl Cyclases, Animals, Animals, Newborn, Hypoxia, Binding, Competitive, Brain Stem, Female, Heart, Mortality, Myocardium, Nicotine, Pregnancy, Prenatal Exposure Delayed Effects, Receptors, Adrenergic, beta, Receptors, Muscarinic, Receptors, Nicotinic, Tritium, Rats, Sprague-Dawley, Nicotinic Agonists, Receptor, Muscarinic M2, Rats
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