Intrarenal perfusion and angiotensin II levels regulate in vivo angiotensin II type 1 receptor imaging in the kidney.
Intrarenal perfusion and angiotensin II levels regulate in vivo angiotensin II type 1 receptor imaging in the kidney.
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肾内灌注和血管紧张素 II 水平调节肾脏体内血管紧张素 II 1 型受体成像。
DOI：
10.1161/hypertensionaha.108.112276
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Zhuo,JiaL
中科院分区：
文献类型：
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作者：
Zhuo,JiaL
在最近一期的《高血压》杂志中，Szabo博士的研究小组使用新型正电子发射断层扫描（PET）[11 C] KR 31173成像研究了体内肾动脉狭窄猪模型中肾内血管紧张素II 1型（AT 1）受体结合的调节。1在这项研究中，通过[11 C] KR 31173（L-159 884）活体成像显示，肾动脉狭窄的猪肾中AT 1受体结合显著增加，并且用ACE抑制剂赖诺普利预处理动物2周不会改变体内AT 1受体结合。1作者将这些结果解释为肾动脉狭窄导致的肾灌注减少增加了体内AT 1受体结合，赖诺普利应消除AT 1受体结合的增加。作者进一步指出，活体PET [11 C] KR 31173成像可能是肾血管疾病患者的诊断生物标志物。然而，肾动脉狭窄被公认为增加循环和肾内Ang II水平，这可能导致血管和肾内AT 1受体下调。2狭窄猪肾脏中[11 C] KR 31173水平升高可能归因于[11 C] KR 31173的清除延迟或肾内蓄积（或保留）增加，因为在研究中，在实时成像前无法分离组织或细胞结合和游离[11 C] KR 31173。1事实上，在注射放射性配体后2分钟时明显观察到[11 C] KR 31173水平显著降低，随后在注射放射性配体后30分钟狭窄的肾脏中[11 C] KR 31173蓄积显著增加。相比之下，大多数注射的[11C] KR 31173在30分钟时已经从正常肾脏和对侧肾脏中消失。1这些图像与肾动脉狭窄的肾脏与对侧肾脏相比肾内灌注减少70%一致。长期赖诺普利治疗并没有改变狭窄猪肾的肾内AT1受体结合，这一发现表明，血管紧张素I转换酶（ACE）在本研究中可能没有得到充分的抑制。1确定这些猪的血浆肾素活性（或浓度）以及循环和肾内Ang II水平是否因长期赖诺普利治疗而改变将是有趣的。这些研究人员确实很好地表明，在高盐或低盐饮食处理的狗中，肾内AT 1受体结合与Ang II呈负相关。3我们先前也表明，在体内大鼠中，硝普钠增加的肾灌注减少，而ACE抑制剂培哚普利增加肾内AT 1受体结合。[4]在小鼠中，长期用卡托普利抑制ACE也增加了受体介导的[125 I]-Val 5-Ang II的细胞内摄取，部分原因是肾内AT 1受体上调。5因此，长期赖诺普利治疗应该增加而不是消除体内肾内AT 1受体结合，如本研究所示。1
In the recent issue of Hypertension, Dr Szabo’s group used novel positron-emission tomographic (PET)[11C] KR31173 imaging to study the regulation of intrarenal angiotensin II type 1 (AT1) receptor binding in a swine model of renal artery stenosis in vivo. 1 In this study, AT1 receptor binding, as visualized by live [11C] KR31173 imaging (L-159 884), was markedly increased in pig kidneys with renal artery stenosis, and pretreatment of the animals with the ACE inhibitor lisinopril for 2 weeks did not alter AT1 receptor binding in vivo. 1 The authors interpreted these results as that reduced renal perfusion attributable to renal artery stenosis increases AT1 receptor binding in vivo and that lisinopril should abolish this increase in AT1 receptor binding. The authors further suggest that live PET [11C] KR31173 imaging may be a diagnostic biomarker for patients with renovascular disease. However, renal artery stenosis is well-recognized to increase circulating and intrarenal Ang II levels, which may lead to the downregulation of vascular and intrarenal AT1 receptors. 2 Increased [11C] KR31173 levels in pig kidneys with stenosis were likely attributable to delayed clearance or increased intrarenal accumulation (or retention) of [11C] KR31173, because tissue-or cell-bound and free [11C] KR31173 could not be separated before live imaging in the study. 1 Indeed, marked decreases in [11C] KR31173 levels were clearly observed at 2 minutes, which were followed by marked increases in [11C] KR31173 accumulation in the kidneys with stenosis at 30 minutes after injection of the radioligand. By contrast, most injected [11C] KR31173 already disappeared from normal kidneys and contralateral kidneys at 30 minutes. 1 These images were consistent with 70% reductions in intrarenal perfusion in the kidneys with renal artery stenosis compared with contralateral kidneys. The finding that long-term lisinopril treatment did not alter intrarenal AT1 receptor binding in pig kidneys with stenosis suggests that angiotensin I–converting enzyme (ACE) might not be adequately inhibited in this study. 1 It would be interesting to determine whether plasma renin activities (or concentrations) and circulating and intrarenal Ang II levels in these pigs were altered by long-term lisinopril treatment. These investigators have indeed nicely showed that intrarenal AT1 receptor binding was inversely related to Ang II in dogs treated with high-or low-salt diet. 3 We also previously showed that increased renal perfusion by sodium nitroprusside decreased, whereas the ACE inhibitor perindopril increased, intrarenal AT1 receptor binding in rats in vivo. 4 Long-term ACE inhibition with captopril also increased receptor-mediated intracellular uptake of [125I]-Val5-Ang II in mice in part because of the upregulation of intrarenal AT1 receptors. 5 Thus, long-term lisinopril treatment should increase rather than abolish intrarenal AT1 receptor binding in vivo, as suggested by this study. 1