Bell J M, Whitmore W L, Slotkin T A
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Pediatr Res. 1988 Apr;23(4):423-7. doi: 10.1203/00006450-198804000-00017.
To determine the mechanisms by which neuronal input influences cardiac growth during altered neonatal nutritional status, rats were reared in small, standard, or large litter sizes and the adrenergically mediated stimulation of cardiac ornithine decarboxylase was determined; ornithine decarboxylase provides a mechanistic link connecting adrenergic input to cardiac growth. Nutritionally deprived pups showed impaired development of sympathetic reflex stimulation as shown by the attenuation of the cardiac ornithine decarboxylase response to hydralazine-induced hypotension throughout the preweanling period. The subnormal reactivity to hydralazine reflected a defect in neurotransmission, as a full response was obtained with direct beta-receptor stimulation (isoproterenol). Nevertheless, cardiac hypertrophy in response to repeated isoproterenol administration was markedly suppressed in nutritionally deprived animals, suggesting that the beta-receptor/ornithine decarboxylase pathway had become uncoupled from growth. Because maturation of neural connections to peripheral tissues causes a loss of hypoxia tolerance, nutritional status also influenced the ability of neonatal rats to survive hypoxia. These data indicate that cardiac growth suppression or enhancement caused by nutritional manipulations may be mediated, in part, through alterations in the development of neuronal input to the tissue, and that similar factors influence survival during hypoxic stress.
为了确定在新生儿营养状况改变期间神经元输入影响心脏生长的机制，将大鼠饲养在小、标准或大窝仔数环境中，并测定肾上腺素能介导的心脏鸟氨酸脱羧酶刺激；鸟氨酸脱羧酶提供了一个将肾上腺素能输入与心脏生长联系起来的机制性环节。营养缺乏的幼崽表现出交感反射刺激发育受损，这在整个断奶前期对肼屈嗪诱导的低血压时心脏鸟氨酸脱羧酶反应的减弱中得到体现。对肼屈嗪反应性低下反映了神经传递缺陷，因为直接β受体刺激（异丙肾上腺素）可获得完全反应。然而，在营养缺乏的动物中，反复给予异丙肾上腺素后心脏肥大明显受到抑制，这表明β受体/鸟氨酸脱羧酶途径已与生长解偶联。由于神经与外周组织连接的成熟会导致缺氧耐受性丧失，营养状况也影响新生大鼠对缺氧的存活能力。这些数据表明，营养操作引起的心脏生长抑制或增强可能部分是通过组织神经元输入发育的改变介导的，并且类似因素影响缺氧应激期间的存活。
