Prieto-Carrasquero Minolfa C, Botros Fady T, Pagan Javier, Kobori Hiroyuki, Seth Dale M, Casarini Dulce E, Navar L Gabriel
Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, La. 70112, USA.
Hypertension. 2008 Jun;51(6):1590-6. doi: 10.1161/HYPERTENSIONAHA.108.110916. Epub 2008 Apr 21.
Renin in collecting duct cells is upregulated in chronic angiotensin II-infused rats via angiotensin II type 1 receptors. To determine whether stimulation of collecting duct renin is a blood pressure-dependent effect; changes in collecting duct renin and associated parameters were assessed in both kidneys of 2-kidney, 1-clip Goldblatt hypertensive (2K1C) rats. Renal medullary tissues were used to avoid the contribution of renin from juxtaglomerular cells. Systolic blood pressure increased to 184+/-9 mm Hg in 2K1C rats (n=19) compared with sham rats (121+/-6 mm Hg; n=12). Although renin immunoreactivity markedly decreased in juxtaglomerular cells of nonclipped kidneys (NCK: 0.2+/-0.0 versus 1.0+/-0.0 relative ratio) and was augmented in clipped kidneys (CK: 1.7+/-1.0 versus 1.0+/-0.0 relative ratio), its immunoreactivity increased in cortical and medullary collecting ducts of both kidneys of 2K1C rats (CK: 2.8+/-1.0 cortex; 2.1+/-1.0 medulla; NCK: 4.6+/-2.0 cortex, 3.2+/-1.0 medulla versus 1.0+/-0.0 in sham kidneys). Renal medullary tissues of 2K1C rats showed greater levels of renin protein (CK: 1.4+/-0.2; NCK: 1.5+/-0.3), renin mRNA (CK: 5.8+/-2.0; NCK: 4.9+/-2.0), angiotensin I (CK: 120+/-18 pg/g; NCK: 129+/-13 pg/g versus sham: 67+/-6 pg/g), angiotensin II (CK: 150+/-32 pg/g; NCK: 123+/-21 pg/g versus sham: 91+/-12 pg/g; P<0.05), and renin activity (CK: 8.6 microg of angiotensin I per microgram of protein; NCK: 8.3 microg of angiotensin I per microgram of protein; sham: 3.4 microg of angiotensin I per microgram of protein) than sham rats. These data indicate that enhanced collecting duct renin in 2K1C rats occurs independently of blood pressure. Upregulation of distal tubular renin helps to explain how sustained intrarenal angiotensin II formation occurs even during juxtaglomerular renin suppression, thus allowing maintained effects on tubular sodium reabsorption that contribute to the hypertension.
在慢性输注血管紧张素II的大鼠中，集合管细胞中的肾素通过1型血管紧张素II受体上调。为了确定集合管肾素的刺激是否是血压依赖性效应；在双肾单夹型Goldblatt高血压（2K1C）大鼠的双肾中评估了集合管肾素及相关参数的变化。使用肾髓质组织以避免球旁细胞肾素的影响。与假手术大鼠（121±6 mmHg；n = 12）相比，2K1C大鼠（n = 19）的收缩压升至184±9 mmHg。虽然未夹闭肾脏（NCK）的球旁细胞中肾素免疫反应性显著降低（相对比值：0.2±0.0对1.0±0.0），而夹闭肾脏（CK）中则增强（相对比值：1.7±1.0对1.0±0.0），但2K1C大鼠双肾的皮质和髓质集合管中肾素免疫反应性增加（CK：皮质2.8±1.0；髓质2.1±1.0；NCK：皮质4.6±2.0，髓质3.2±1.0，假手术肾脏为1.0±0.0）。2K1C大鼠的肾髓质组织显示出比假手术大鼠更高水平的肾素蛋白（CK：1.4±0.2；NCK：1.5±0.3）、肾素mRNA（CK：5.8±2.0；NCK：4.9±2.0）、血管紧张素I（CK：120±18 pg/g；NCK：129±13 pg/g，假手术：67±6 pg/g）、血管紧张素II（CK：150±32 pg/g；NCK：123±21 pg/g，假手术：91±12 pg/g；P<0.05）和肾素活性（CK：每微克蛋白8.6微克血管紧张素I；NCK：每微克蛋白8.3微克血管紧张素I；假手术：每微克蛋白3.4微克血管紧张素I）。这些数据表明，2K1C大鼠中集合管肾素增强独立于血压发生。远曲小管肾素的上调有助于解释即使在球旁肾素受抑制期间肾内血管紧张素II的持续形成是如何发生的，从而使对肾小管钠重吸收的持续作用得以维持，这有助于高血压的形成。
