Lütken Sophie Constantin, Frøkiær Jørgen, Nielsen Søren
Department of Biomedicine -Anatomy, University of Aarhus, DK-8000 Aarhus C, Denmark; Institute of Clinical Medicine, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.
Institute of Clinical Medicine, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.
PLoS One. 2015 Feb 6;10(2):e0116501. doi: 10.1371/journal.pone.0116501. eCollection 2015.
The objective was to examine the renal effects of long-term increased angiotensin II and vasopressin plasma levels in early-stage heart failure (HF). We investigated the regulations of the V2 vasopressin receptor, the type 1A angiotensin II receptor, the (pro)renin receptor, and the water channels AQP2, AQP1, AQP3, and AQP4 in the inner medulla of rat kidney.
HF was induced by coronary artery ligation. Sixty-eight rats were allocated to six groups: Sham (N = 11), HF (N = 11), sodium restricted sham (N = 11), sodium restricted HF (N = 11), sodium restricted sham + DDAVP (N = 12), and sodium restricted HF + DDAVP (N = 12). 1-desamino-8-D-arginine vasopressin (0.5 ng h-1 for 7 days) or vehicle was administered. Pre- and post-treatment echocardiographic evaluation was performed. The rats were sacrificed at day 17 after surgery, before cardiac remodeling in rat is known to be completed.
HF rats on standard sodium diet and sodium restriction displayed biochemical markers of HF. These rats developed hyponatremia, hypo-osmolality, and decreased fractional excretion of sodium. Increase of AQP2 and p(Ser256)-AQP2 abundance in all HF groups was blunted compared with control groups even when infused with DDAVP and despite increased vasopressin V2 receptor and Gsα abundance. This was associated with decreased protein abundance of the AT1A receptor in HF groups vs. controls.
Early-stage HF is associated with blunted increase in AQP2 and p(Ser256)-AQP2 despite of hyponatremia, hypo-osmolality, and increased inner medullary vasopressin V2 receptor expression. Decreased type 1A angiotensin II receptor abundance likely plays a role in the transduction of these effects.
本研究旨在探讨早期心力衰竭（HF）患者长期血管紧张素II和血管加压素血浆水平升高对肾脏的影响。我们研究了大鼠肾内髓质中V2血管加压素受体、1A型血管紧张素II受体、（前）肾素受体以及水通道蛋白AQP2、AQP1、AQP3和AQP4的调控情况。
通过冠状动脉结扎诱导心力衰竭。将68只大鼠分为六组：假手术组（N = 11）、心力衰竭组（N = 11）、限钠假手术组（N = 11）、限钠心力衰竭组（N = 11）、限钠假手术 + 去氨加压素组（N = 12）和限钠心力衰竭 + 去氨加压素组（N = 12）。给予1-去氨基-8-D-精氨酸血管加压素（0.5 ng·h-1，持续7天）或赋形剂。在治疗前后进行超声心动图评估。术后第17天处死大鼠，此时大鼠心脏重塑尚未完成。
标准钠饮食和限钠的心力衰竭大鼠出现了心力衰竭的生化标志物。这些大鼠出现低钠血症、低渗血症和钠排泄分数降低。与对照组相比，所有心力衰竭组中AQP2和p(Ser256)-AQP2丰度的增加均受到抑制，即使在输注去氨加压素的情况下，尽管血管加压素V2受体和Gsα丰度增加。这与心力衰竭组与对照组相比AT1A受体蛋白丰度降低有关。
尽管存在低钠血症、低渗血症和肾内髓质血管加压素V2受体表达增加，但早期心力衰竭与AQP2和p(Ser256)-AQP2的增加受到抑制有关。1A型血管紧张素II受体丰度降低可能在这些效应的传导中起作用。
