Physiologisches Institut, Universität Regensburg, D-93053 Regensburg, Germany.
Am J Physiol Renal Physiol. 2012 May 15;302(10):F1278-85. doi: 10.1152/ajprenal.00688.2011. Epub 2012 Feb 22.
The salt intake of an organism controls the number of renin-producing cells in the kidney by yet undefined mechanisms. This study aimed to assess a possible mediator role of preglomerular blood pressure in the control of renin expression by oral salt intake. We used wild-type (WT) mice and mice lacking angiotensin II type 1a receptors (AT(1a)-/-) displaying an enhanced salt sensitivity to renin expression. In WT kidneys, we found renin-expressing cells at the ends of all afferent arterioles. A low-salt diet (0.02%) led to a moderate twofold increase in renin-expressing cells along afferent arterioles. In AT(1a)-/- mice, lowering of salt content led to a 12-fold increase in renin expression. Here, the renin-expressing cells were distributed along the preglomerular vascular tree in a typical distal-to-proximal distribution gradient which was most prominent at high salt intake and was obliterated at low salt intake by the appearance of renin-expressing cells in proximal parts of the preglomerular vasculature. While lowering of salt intake produced only a small drop in blood pressure in WT mice, the marked reduction of systolic blood pressure in AT(1a)-/- mice was accompanied by the disappearance of the distribution gradient from afferent arterioles to arcuate arteries. Unilateral renal artery stenosis in AT(1a)-/- mice on a normal salt intake produced a similar distribution pattern of renin-expressing cells as did low salt intake. Conversely, increasing blood pressure by administration of the NOS inhibitor N-nitro-l-arginine methyl ester or of the adrenergic agonist phenylephrine in AT(1a)-/- mice kept on low salt intake produced a similar distribution pattern of renin-producing cells as did normal salt intake alone. These findings suggest that changes in preglomerular blood pressure may be an important mediator of the influence of salt intake on the number and distribution of renin-producing cells in the kidney.
机体的盐摄入量通过尚未明确的机制控制肾脏中产生肾素的细胞数量。本研究旨在评估肾小球前血压在盐摄入控制肾素表达中的可能介导作用。我们使用野生型（WT）小鼠和缺乏血管紧张素 II 型 1a 受体（AT(1a)-/-）的小鼠，这些小鼠对肾素表达表现出增强的盐敏感性。在 WT 肾脏中，我们发现肾素表达细胞位于所有入球小动脉的末端。低盐饮食（0.02%）导致沿入球小动脉的肾素表达细胞适度增加两倍。在 AT(1a)-/-小鼠中，降低盐含量导致肾素表达增加 12 倍。在这里，肾素表达细胞沿肾小球前血管树呈典型的从远端到近端的分布梯度分布，在高盐摄入时最为明显，而在低盐摄入时，由于近端肾小球前血管中出现肾素表达细胞，这种分布梯度消失。虽然盐摄入降低仅使 WT 小鼠的血压略有下降，但 AT(1a)-/- 小鼠的收缩压显著降低伴随着从入球小动脉到弓状动脉的分布梯度的消失。在正常盐摄入的 AT(1a)-/- 小鼠中单侧肾动脉狭窄产生与低盐摄入相同的肾素表达细胞分布模式。相反，在低盐摄入的 AT(1a)-/- 小鼠中通过给予一氧化氮合酶抑制剂 N-硝基-L-精氨酸甲酯或肾上腺素能激动剂苯肾上腺素来增加血压会产生与正常盐摄入单独相同的肾素产生细胞分布模式。这些发现表明，肾小球前血压的变化可能是盐摄入对肾脏中肾素产生细胞数量和分布的影响的重要介导因素。
