Urotensin II and renal insufficiency in growth-restricted infants.

胎儿宫内生长受限(IUGR)与围产期器官损伤及发生风险相关 晚年的心血管、肾脏和代谢紊乱。因此，阐明导致早产的机制 在生长受限的新生儿中进行进行性器官紊乱是必要的，以减少婴儿和成人 发病率和死亡率。尾加压素II(UII)是一种调节肾功能的有效血管活性多肽，其水平为 在患有心脏和肾脏疾病的婴儿中增加。虽然它的生理和病理生理机制 都没有解决，最近的证据表明，UII系统可以促进神经传递，从而改变 器官功能。在这里，我们提出了一个新的概念，即尿路感染活动增加导致肾功能不全。 在生长受限的新生儿中。UII通过钙依赖酪氨酸刺激外周交感神经兴奋 羟基酶的磷酸化、儿茶酚胺的生物合成和神经传递。引发交感神经流出 尿路感染会引发新生儿肾脏损伤。这些概念将在新生猪和临床前研究中进行 自然发生人非对称性宫内发育迟缓的猪模型。使用创新的程序进行翻译 研究方面，我们将研究小于胎龄新生猪的肾功能，并阐明其功能和 UII系统的调节及其成分在1)新生儿肾脏改变中的作用 血流动力学和2)生长受限婴儿的肾功能不全。我们预计，我们提议的研究将 对了解未成熟肾脏的病理生理学有重要影响。

Intrauterine growth restriction (IUGR) is associated with perinatal organ injury and the risk of developing cardiovascular, renal, and metabolic disorders in later life. Hence, elucidation of the mechanisms that cause early and progressive organ derangement in growth-restricted newborns is necessary to reduce infant and adult morbidity and mortality. Urotensin II (UII), a potent vasoactive peptide modulates renal function, and its levels are increased in infants with heart and kidney disease. Although its physiological and pathophysiological mechanisms are unresolved, recent evidence suggests that the UII system can promote neurotransmission, thereby altering organ function. Here, we propose a new concept that an increase in UII activity contributes to renal insufficiency in growth-restricted newborns. UII stimulates peripheral sympathoexcitation via Ca2+-dependent tyrosine hydroxylase phosphorylation, catecholamine biosynthesis, and neurotransmission. Sympathetic outflow elicited by UII triggers kidney injury in the neonates. These concepts will be investigated in newborn pigs and a preclinical porcine model of naturally-occurring human asymmetric IUGR. Using innovative procedures for translational research, we will study renal function in small-for-gestational-age neonatal pigs and elucidate the function and regulation of the UII system and the contribution of its components to 1) alterations in neonatal renal hemodynamics and 2) renal insufficiency in growth-restricted infants. We anticipate that our proposed studies will have a significant impact on understanding the pathophysiology of the immature kidney.