Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Brazil.
J Renin Angiotensin Aldosterone Syst. 2013 Sep;14(3):271-82. doi: 10.1177/1470320312456328. Epub 2012 Aug 30.
The current study examines changes in the postnatal hypothalamic angiotensin receptors by maternal protein restriction (LP), and its impact on in uteri programming of hypertension in adult life. The data show that LP male pup body weight was significantly reduced when compared to that of control (NP) pups. Also, immunoblotting analysis demonstrated a significantly decreased expression of type 1 AngII receptors (AT1R) in the entire hypothalamic tissue extract of LP rats at 12 days of age compared to age-matched NP offspring. Conversely, the expression of the type 2 AngII (AT2R) receptors in 12-day- and 16-week-old LP hypothalamus was significantly increased. The current data show the influence of central AngII administration on water consumption in a concentration-dependent fashion, but also demonstrate that the water intake response to AngII was strikingly attenuated in 16-week-old LP. These results may be related to decreased brain arginine vasopressin (AVP) expression appearing in maternal protein-restricted offspring. The present investigation shows an early decrease in fractional urinary sodium excretion in maternal protein-restricted offspring. The decreased fractional sodium excretion was accompanied by a fall in proximal sodium excretion and occurred despite unchanged creatinine clearance. These effects were associated with a significant enhancement in arterial blood pressure in the LP group, but the precise mechanism of these phenomena remains unknown.
本研究通过母体蛋白质限制(LP)观察产后下丘脑血管紧张素受体的变化及其对成年高血压宫内编程的影响。数据表明,与对照(NP)幼崽相比,LP 雄性幼崽的体重明显减轻。免疫印迹分析还表明,与同龄 NP 后代相比,LP 大鼠在 12 天时整个下丘脑组织提取物中 1 型血管紧张素 II 受体(AT1R)的表达明显降低。相反,12 天和 16 周龄 LP 下丘脑的 2 型血管紧张素 II(AT2R)受体的表达明显增加。目前的数据表明,中枢血管紧张素 II 给药以浓度依赖的方式影响水的消耗,但也表明 16 周龄 LP 对血管紧张素 II 的水摄入反应明显减弱。这些结果可能与出现在母体蛋白质限制后代中的脑精氨酸加压素(AVP)表达减少有关。本研究显示母体蛋白质限制后代的尿钠排泄分数早期下降。尽管肌酐清除率没有变化,但钠排泄分数的降低伴随着近端钠排泄的减少。这些效应与 LP 组的动脉血压显著升高有关,但这些现象的确切机制尚不清楚。