Rico A J, Prieto-Lloret J, Gonzalez C, Rigual R
Departamento de Bioquímica y Biología Molecular y Fisiología, Instituto de Biología y Genética Molecular (IBGM Universidad de Valladolid, Consejo Superior de Investigaciones Científicas, Facultad de Medicina, Calle Ramón y Cajal, 47005 Valladolid, Spain.
Am J Physiol Cell Physiol. 2005 Dec;289(6):C1417-25. doi: 10.1152/ajpcell.00023.2005. Epub 2005 Aug 10.
Hypoxia elicits catecholamine (CA) secretion from the adrenal medulla (AM) in perinatal animals by acting directly on chromaffin cells. However, whether innervation of the AM, which in the rat occurs in the second postnatal week, suppresses this direct hypoxic response is the subject of debate. Opioid peptides have been proposed as mediators of this suppression. To resolve these controversies, we have compared CA-secretory responses with high external concentrations of K+ ([K+]e) and hypoxia in the AM of neonatal (1- to 2-day-old) and juvenile (14- or 15- and 30-day-old) rats subjected to superfusion in vitro. In addition, we studied the effect of hypercapnic acidosis on the CA-secretory responses in the AM during postnatal development and the possible interaction between acidic and hypoxic stimuli. Responses to high [K+]e were comparable at all ages, but responses to hypoxia and hypercapnic acidosis were maximal in neonatal animals. Suppression of the hypoxic response in the rat AM was not mediated by opioids, because their agonists did not affect the hypoxic CA response. The association of hypercapnic acidosis and hypoxia, mimicking the episodes of asphyxia occurring during delivery, generates a more than additive secretory response in the neonatal rat AM. Our data confirm the loss of the direct sensitivity to hypoxia of the AM in the initial weeks of life and demonstrate a direct response of neonatal AM to hypercapnic acidosis. The synergistic effect of hypoxia and acidosis would explain the CA outburst crucial for adaptation to extrauterine life observed in naturally delivered mammals.
缺氧通过直接作用于嗜铬细胞，引发围产期动物肾上腺髓质（AM）分泌儿茶酚胺（CA）。然而，AM的神经支配在大鼠出生后第二周出现，它是否会抑制这种直接的缺氧反应仍存在争议。阿片肽被认为是这种抑制作用的介质。为了解决这些争议，我们比较了体外灌注的新生（1至2日龄）和幼年（14或15日龄以及30日龄）大鼠AM对高细胞外钾浓度（[K+]e）和缺氧的CA分泌反应。此外，我们研究了高碳酸血症酸中毒对出生后发育过程中AM的CA分泌反应的影响，以及酸性和缺氧刺激之间可能的相互作用。对高[K+]e的反应在所有年龄段都相当，但对缺氧和高碳酸血症酸中毒的反应在新生动物中最大。大鼠AM中缺氧反应的抑制不是由阿片类物质介导的，因为它们的激动剂不影响缺氧时的CA反应。高碳酸血症酸中毒与缺氧的联合作用，模拟了分娩过程中发生的窒息发作，在新生大鼠AM中产生了超过相加的分泌反应。我们的数据证实了出生后最初几周AM对缺氧的直接敏感性丧失，并证明了新生AM对高碳酸血症酸中毒的直接反应。缺氧和酸中毒的协同作用可以解释自然分娩的哺乳动物中观察到的对宫外生活适应至关重要的CA爆发。
