(Pro) renin receptor peptide inhibitor "handle-region" peptide does not affect hypertensive nephrosclerosis in Goldblatt rats
(Pro) renin receptor peptide inhibitor "handle-region" peptide does not affect hypertensive nephrosclerosis in Goldblatt rats
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DOI：
10.1161/hypertensionaha.107.101493
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发表时间：
2008-03-01
期刊：
影响因子：
8.3
通讯作者：
Hilgers, Karl F.
中科院分区：
文献类型：
--
作者：
Muller, Dominik N.;Klanke, Bernd;Hilgers, Karl F.
（P）RR是新近克隆的一种新的肾素-血管紧张素系统组分。（P）RR促进直接丝裂原活化蛋白激酶信号传导和非蛋白水解性前肾素活化。我们研究了（P）RR阻断剂（一种由10个氨基酸组成的肽，来自被称为“HRP区”肽（HRP）的前体部分）对肾血管性高血压2肾1夹（2K 1C）大鼠靶器官损伤的作用。将溶剂处理的2K 1C大鼠与HRP处理的2K 1C大鼠（3.5 μ g/kg/天）和假手术对照组进行比较。溶剂处理的2K 1C大鼠出现高血压（186 +/- 17 mm Hg）、心脏肥大（3.16 +/- 0.16 mg/g）、肾脏炎症、纤维化、血管和肾小管损伤。长期HRP治疗不影响血压（194 +/- 15 mm Hg）、心脏肥大（2.97 +/- 0.11 mg/g）或肾损伤。此外，我们还研究了肾组织中的肾素和（P）RR表达。与假手术组相比，2K 1C和HRP处理的2K 1C大鼠的肾脏显示出更高的肾素表达和肾小球指数。未夹闭的肾脏显示出抑制的肾素表达。相反，（P）RR mRNA表达在任何组中均未改变。与假手术对照组相比，2K 1C大鼠血浆肾素活性和醛固酮升高。HRP治疗的2K 1C大鼠倾向于降低血浆肾素活性，但表现出与溶剂治疗的2K 1C大鼠相似的醛固酮水平。我们的结果表明，阻断（P）RR与HRP并没有改善肾血管性高血压大鼠的靶器官损害。
The (pro) renin receptor [(P) RR], a new component the renin-angiotensin system, was cloned recently. The (P) RR promotes direct mitogen-activated protein kinase signaling and nonproteolytic prorenin activation. We investigated the role of a (P) RR blocker, a peptide consisting of 10 amino acids from the prorenin prosegment called the "handle-region" peptide (HRP), on target organ damage in renovascular hypertensive 2-kidney, 1-clip (2K1C) rats. Vehicle-treated 2K1C rats were compared with HRP-treated 2K1C rats (3.5 mu g/kg per day) and sham-operated controls. Vehicle-treated 2K1C rats developed hypertension (186 +/- 17 mm Hg), cardiac hypertrophy (3.16 +/- 0.16 mg/g), renal inflammation, fibrosis, vascular, and tubular damage. Chronic HRP treatment did not affect blood pressure (194 +/- 15 mm Hg), cardiac hypertrophy (2.97 +/- 0.11 mg/g), or renal damage. Furthermore, we investigated the renal renin and (P) RR expression. The clipped kidney of 2K1C and HRP-treated 2K1C rats showed a higher renin expression and juxtaglomerular index compared with sham-operated kidneys. The unclipped kidney showed suppressed renin expression. In contrast, (P) RR mRNA expression was not altered in any group. Plasma renin activity and aldosterone were increased in 2K1C rats compared with sham controls. HRP-treated 2K1C rats tended to lower plasma renin activity but showed similar aldosterone levels as vehicle-treated 2K1C rats. Our results indicate that blockade of the (P) RR with HRP does not improve target organ damage in renovascular hypertensive rats.