Liggins Institute and Gravida, National Centre for Growth and Development, University of Auckland, Auckland, New Zealand.
PLoS One. 2013;8(1):e53505. doi: 10.1371/journal.pone.0053505. Epub 2013 Jan 7.
Maternal undernutrition results in elevated blood pressure (BP) and endothelial dysfunction in adult offspring. However, few studies have investigated interventions during early life to ameliorate the programming of hypertension and vascular disorders. We have utilised a model of maternal undernutrition to examine the effects of pre-weaning growth hormone (GH) treatment on BP and vascular function in adulthood. Female Sprague-Dawley rats were fed either a standard control diet (CON) or 50% of CON intake throughout pregnancy (UN). From neonatal day 3 until weaning (day 21), CON and UN pups received either saline (CON-S, UN-S) or GH (2.5 ug/g/day)(CON-GH, UN-GH). All dams were fed ad libitum throughout lactation. Male offspring were fed a standard diet until the end of the study. Systolic blood pressure (SBP) was measured at day 150 by tail cuff plethysmography. At day 160, intact mesenteric vessels mounted on a pressure myograph. Responses to pressure, agonist-induced constriction and endothelium-dependent vasodilators were investigated to determine vascular function. SBP was increased in UN-S groups and normalised in UN-GH groups (CON-S 121±2 mmHg, CON-GH 115±3, UN-S 146±3, UN-GH 127±2). Pressure mediated dilation was reduced in UN-S offspring and normalised in UN-GH groups. Vessels from UN-S offspring demonstrated a reduced constrictor response to phenylephrine and reduced vasodilator response to acetylcholine (ACh). Furthermore, UN-S offspring vessels displayed a reduced vasodilator response in the presence of L-NG-Nitroarginine Methyl Ester (L-NAME), carbenoxolone (CBX), L-NAME and CBX, Tram-34 and Apamin. UN-GH vessels showed little difference in responses when compared to CON and significantly increased vasodilator responses when compared to UN-S offspring. Pre-weaning GH treatment reverses the negative effects of maternal UN on SBP and vasomotor function in adult offspring. These data suggest that developmental cardiovascular programming is potentially reversible by early life GH treatment and that GH can reverse the vascular adaptations resulting from maternal undernutrition.
母体营养不良会导致成年后代血压升高和内皮功能障碍。然而，很少有研究探讨过在生命早期进行干预以改善高血压和血管疾病的编程。我们利用母体营养不良模型研究了在断奶前给予生长激素（GH）治疗对成年后血压和血管功能的影响。雌性 Sprague-Dawley 大鼠在整个怀孕期间均喂食标准对照饮食（CON）或摄入 50%CON （UN）。从出生后第 3 天到断奶（第 21 天），CON 和 UN 幼崽分别接受生理盐水（CON-S，UN-S）或 GH（2.5ug/g/天）（CON-GH，UN-GH）治疗。所有母鼠在哺乳期均自由进食。雄性后代在研究结束前喂食标准饮食。通过尾套测压法在第 150 天测量收缩压（SBP）。在第 160 天，将完整的肠系膜血管安装在压力肌动描记器上。通过测量血管对压力、激动剂诱导的收缩和内皮依赖性血管舒张剂的反应来研究血管功能。UN-S 组的 SBP 升高，而 UN-GH 组的 SBP 正常（CON-S 为 121±2mmHg，CON-GH 为 115±3mmHg，UN-S 为 146±3mmHg，UN-GH 为 127±2mmHg）。UN-S 后代的血管介导的舒张功能降低，而 UN-GH 组的舒张功能正常。来自 UN-S 后代的血管对苯肾上腺素的收缩反应减弱，对乙酰胆碱（ACh）的舒张反应减弱。此外，在 L-NG-硝基精氨酸甲酯（L-NAME）、卡波酮（CBX）、L-NAME 和 CBX、Tram-34 和 Apamin 存在的情况下，UN-S 后代的血管舒张反应降低。与 CON 相比，UN-GH 血管的反应差异不大，与 UN-S 后代相比，其血管舒张反应显著增加。在断奶前给予 GH 治疗可逆转母体 UN 对成年后代 SBP 和血管舒缩功能的负面影响。这些数据表明，通过早期生命 GH 治疗可以潜在地逆转发育性心血管编程，并且 GH 可以逆转母体营养不良引起的血管适应。
