Chronic nicotine in utero selectively suppresses hypoxic sensitivity in neonatal rat adrenal chromaffin cells

Nicotine in cigarette smoke has been linked to several deleterious side effects on the off spring of smoking mothers, including impaired devel opment of the sympathoadrenal system, abnormal arousal reflexes, and sudden infant death syndrome. Catecholamine (CA) release from adrenomedullary chromaffin cells (AMCs) in response to asphyxial stres sors, e.g., low O 2 (hypoxia) and elevated CO 2 (hyper capnia), is critical for adaptation to extrauterine life and occurs before splanchnic innervation. Here, we investigated the effects of prenatal nicotine bitartrate exposure on the ability of neonatal (P0) rat AMCs to respond appropriately to asphyxial stressors. Control AMCs isolated from pups born to saline‐treated dams displayed typical responses to hypoxia and hypercap nia, including inhibition of outward K + current, mem brane depolarization, increased cytosolic calcium, and CA secretion. In contrast, P0 AMCs from pups born to nicotine‐treated dams showed a marked suppression or loss of hypoxic sensitivity, although hypercapnic sensi tivity and the expression of CO 2 markers (i.e., carbonic anhydrase I and II) appeared normal. Moreover, iso lated saline‐treated P0 AMCs lost their hypoxic sensi tivity when grown in culture for ~ 1 wk in the presence of a subsaturating concentration of nicotine base (50 μ M), and this effect was abolished by the nicotinic acetylcholine receptor (nAChR) blocker mecamylamine (100 μ M). Taken together, these data suggest that the adverse effects of maternal smoking on sympathoadre nal function in the offspring are due in part to a loss or suppression of acute hypoxic sensitivity in adrenal chromaffin cells, triggered by the direct action of nicotine on endogenous nicotinic acetylcholine receptors.—Buttigieg, J., Brown, S., Zhang, M., Lowe, M., Holloway, A. C., Nurse, C. A. Chronic nicotine in utero selectively suppresses hypoxic sensitivity in neonatal rat adrenal chromaffin cells. FASEB J . 22, 1317–1326 (2008)