Department of Physiology, University of Murcia, Regional Campus of International Excellence "Mare Nostrum," Murcia, Instituto Murciano de Investigación Biomédica, Spain; and.
Anatomisches Institut, Charité, Humboldt Universität, Berlin, Germany.
Am J Physiol Renal Physiol. 2014 Aug 15;307(4):F461-70. doi: 10.1152/ajprenal.00198.2014. Epub 2014 Jun 18.
Numerous studies have evaluated blood pressure (BP) and renal changes in several models of developmental programming of hypertension. The present study examined to what extent BP, renal hemodynamic, and renal structure are affected at an old age in male and female animals with altered renal development. It also evaluated whether renal damage is associated with changes in cyclooxygenase (COX)-2 and neuronal nitric oxide synthase (NOS1) expression and immunoreactivity. Experiments were carried out in rats at 10-11 and 16-17 mo of age treated with vehicle or an ANG II type 1 receptor antagonist during the nephrogenic period (ARAnp). A progressive increment in BP and a deterioration of renal hemodynamics were found in both sexes of ARAnp-treated rats, with these changes being greater (P < 0.05) in male rats. The decrease in glomerular filtration rate at the oldest age was greater (P < 0.05) in male (74%) than female (32%) ARAnp-treated rats. Sex-dependent deterioration of renal structure was demonstrated in optical and electron microscopic experiments. COX-2 and NOS1 immunoreactivity were enhanced in the macula densa of male but not female ARAnp-treated rats. The present study reports novel findings suggesting that stimuli that induce a decrease of ANG II effects during renal development lead to a progressive increment in BP and renal damage at an old age in both sexes, but these BP and renal changes are greater in males than in females. The renal damage is associated with an increase of COX-2 and NOS1 in the macula densa of males but not females with altered renal development.
许多研究已经评估了高血压发展编程的几种模型中的血压 (BP) 和肾脏变化。本研究旨在探讨在改变肾脏发育的雄性和雌性动物中，老年时 BP、肾脏血液动力学和肾脏结构受到多大程度的影响。它还评估了肾脏损伤是否与环氧化酶 (COX)-2 和神经元型一氧化氮合酶 (NOS1) 表达和免疫反应性的变化有关。在接受 vehicle 或血管紧张素 II 型 1 受体拮抗剂 (ARAnp) 治疗的大鼠中，在 10-11 个月和 16-17 个月大时进行了实验。在 ARAnp 处理的大鼠的两性中均发现 BP 逐渐升高和肾脏血液动力学恶化，这些变化在雄性大鼠中更为明显 (P < 0.05)。在最老的年龄时，肾小球滤过率的下降在雄性 (74%) ARAnp 处理的大鼠中比雌性 (32%) ARAnp 处理的大鼠中更为明显 (P < 0.05)。光学和电子显微镜实验证明了肾脏结构的性别依赖性恶化。在雄性而非雌性 ARAnp 处理的大鼠中，致密斑的 COX-2 和 NOS1 免疫反应性增强。本研究报告了新的发现，表明在肾脏发育过程中诱导降低 ANG II 作用的刺激会导致两性在老年时 BP 逐渐升高和肾脏损伤，但这些 BP 和肾脏变化在雄性中比在雌性中更为明显。肾脏损伤与改变肾脏发育的雄性而不是雌性的致密斑中 COX-2 和 NOS1 的增加有关。
