Effects of endothelin-A receptor antagonism on bilateral renal function in renovascular hypertensive rats.
Effects of endothelin-A receptor antagonism on bilateral renal function in renovascular hypertensive rats.
复制标题
内皮素A受体拮抗剂对肾血管性高血压大鼠双侧肾功能的影响。
DOI：
10.1046/j.1472-8206.2001.xs052.x
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发表时间：
2001
影响因子：
2.9
通讯作者：
Granger,JP
中科院分区：
文献类型：
--
作者：
Kassab,S;Hamdy,H;AbdulGhaffar,T;Granger,JP
最近的研究表明，在两肾一夹（2K‐1C）Goldblatt高血压中，血管夹对侧肾脏中内皮素（ET）的表达增强。我们认为，肾内ET产生的增加可能是2K‐1C肾血管性高血压大鼠未夹肾（UK）血流动力学和排泄能力改变的原因。因此，我们同时检查了夹闭（CK）和UK中动脉压和分裂肾功能的变化，以响应选择性ETA受体阻滞剂（A-127722）的长期给药，从夹闭第4周开始以30mg/kg/天的剂量经口给药3周。 对照组大鼠（n=15）的平均收缩压为177 ± 7 mmHg，治疗组大鼠（n=16）的平均收缩压为164± 9 mmHg，差异无统计学意义。 在英国，对照组和治疗组之间的肾小球滤过率（GFR）、肾血浆流量（RPF）和肾血管阻力（RVR）无差异。然后通过将大鼠分类为中度高血压（MAP <180 mmHg）和重度高血压（MAP> 180 mmHg）来分析数据。 在中度高血压组中，对照组（n=9）和治疗组（n=10）的平均MAP分别为143± 5 mmHg和138 ± 4 mmHg。 在重度高血压组中，对照组（n=6）和治疗组（n =6）的平均MAP分别为192± 5 mmHg和188 ± 5 mmHg。 在英国，只有接受拮抗剂治疗的重度高血压患者的GFR和RPF显著改善。而ETA拮抗剂则可抑制高血压大鼠CK和UK的钠丢失。我们得出结论，ETA受体在2K‐1C肾血管性高血压大鼠的高血压进展中不起作用。然而，ETA受体在严重程度的肾血管性高血压中改变未夹闭肾脏的肾血流动力学中起重要作用。
Recent studies indicated an enhanced expression of Endothelin (ET) in the kidney contralateral to the vascular clip in two‐kidney, one‐clip (2K‐1C) Goldblatt hypertension. We proposed that the enhanced intrarenal ET production might be responsible for altered haemodynamic and excretory capability of the unclipped kidney (UK) of 2K‐1C renovascular hypertensive rats. Therefore, we examined the changes in arterial pressure and split renal function in the clipped (CK) and UK simultaneously, in response to chronic administration of the selective ETAreceptor blocker (A‐127722), given orally at a dose of 30 mg/kg/day for 3 weeks starting from the beginning of the 4th week of clipping. Systolic pressure averaged 177 ± 7 mmHg in control rats (n=15) and 164 ± 9 mmHg in treated rats (n=16) and the difference was not statistically different. Glomerular filtration rate (GFR), renal plasma flow (RPF) and renal vascular resistance (RVR) in the UK were not different between control and treated groups. Data were then analyzed by classifying rats as moderate hypertensives (MAP < 180 mmHg), and severe hypertensives (MAP > 180 mmHg). In the moderately hypertensive group, average MAP was 143 ± 5 mmHg and 138 ± 4 mmHg in control (n=9) and treated (n=10) groups, respectively. In the severely hypertensive group, average MAP was 192 ± 5 mmHg and 188 ± 5 mmHg in control (n=6) and treated (n=6) groups, respectively. GFR and RPF were significantly improved in the UK of only the severely hypertensives who received the antagonist. However, the ETAantagonist blunted the sodium loss in both CK and UK of severely hypertensive rats. We conclude that ETAreceptors do not play a role in the progression of hypertension in 2K‐1C renovascular hypertensive rats. Yet, ETAreceptors play an important role in altering renal hemodynamics of the unclipped kidneys in severe degrees of renovascular hypertension.