Pereira-Acácio Amaury, Veloso-Santos João P M, Alves-Bezerra Danilo S, Costa-Sarmento Glória, Muzi-Filho Humberto, Vieyra Adalberto
Graduate Program in Translational Biomedicine/BIOTRANS, UNIGRANRIO University, Duque de Caxias, Brazil; Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Biochem Biophys Res Commun. 2025 Sep 1;777:152295. doi: 10.1016/j.bbrc.2025.152295. Epub 2025 Jul 3.
Undernutrition and hypertension are growing health challenges worldwide. The renin-angiotensin-aldosterone system (RAAS) is frequently altered in these morbidities, and information regarding possible changes in the responses mediated by the angiotensin II (Ang II) type 2 receptor (ATR) pathways in chronic malnutrition is scarce. Normonourished and chronically undernourished rats were used. Undernutrition (and low weight gain) was induced by feeding male Wistar rats a multideficient diet that mimics those consumed in vast regions of developing countries (the Regional Basic Diet/RBD). The main objective of this study was to compare effects on the ATR axis following a single dose or repeated doses of Angiotensin-(3-4) (Ang-(3-4)), its allosteric activator. Na/energy relationships (Na density) were calculated from Na intake and food/energy intake; Na and K balances were determined using flame photometry; proximal tubules Na-transporting ATPases assessing ATP hydrolysis; and blood pressure by plethysmography in normonourished and undernourished rats. Administration of Ang-(3-4) for seven days culminates in a highly positive Na balance instead of the near-zero balance that follows a single dose. There was also a shift from different to identical Na density in the two dietary groups and a very negative K balance, especially in the undernourished group. The Na clearance was strongly inhibited by Ang-(3-4) in undernourished animals without modification of the K clearance. Repeated doses of Ang-(3-4) downregulated ouabain-sensitive (Na+K)ATPase and upregulated ouabain-resistant Na-ATPase in proximal tubules instead of recovery to normonourished values of Na-ATPase activity in the undernourished group. Associated with these electrolyte changes, prolonged Ang-(3-4) exerts hypertensive action in normonourished rats and loss of the hypotensive effect in the undernourished hypertensive rats, respectively.
营养不良和高血压在全球范围内对健康构成了日益严峻的挑战。肾素 - 血管紧张素 - 醛固酮系统（RAAS）在这些病症中经常发生改变，而关于慢性营养不良中血管紧张素II（Ang II）2型受体（ATR）途径介导的反应可能变化的信息却很少。本研究使用了营养正常和长期营养不良的大鼠。通过给雄性Wistar大鼠喂食模拟发展中国家广大地区所食用的多种营养素缺乏的饮食（区域基础饮食/RBD）来诱导营养不良（以及低体重增加）。本研究的主要目的是比较单次或重复剂量的血管紧张素 -（3 - 4）（Ang -（3 - 4））及其变构激活剂对ATR轴的影响。根据钠摄入量和食物/能量摄入量计算钠/能量关系（钠密度）；使用火焰光度法测定钠和钾平衡；通过评估ATP水解来测定近端小管钠转运ATP酶；并通过体积描记法测量营养正常和营养不良大鼠的血压。连续七天给予Ang -（3 - 4）会导致钠平衡高度正向，而不是单次给药后接近零的平衡。两个饮食组的钠密度也从不同转变为相同，并且钾平衡非常负，尤其是在营养不良组中。在营养不良的动物中，Ang -（3 - 4）强烈抑制钠清除率，而钾清除率没有改变。重复剂量的Ang -（3 - 4）会下调近端小管中哇巴因敏感的（Na + K）ATP酶，并上调哇巴因抗性的钠ATP酶，而不是使营养不良组的钠ATP酶活性恢复到营养正常的值。与这些电解质变化相关，延长给予Ang -（3 - 4）分别在营养正常的大鼠中发挥高血压作用，而在营养不良的高血压大鼠中失去降压作用。
