Ismail Basma, deKemp Robert A, Hadizad Tayebeh, Mackasey Kumiko, Beanlands Rob S, DaSilva Jean N
National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, K1Y 4W7, Canada.
Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
EJNMMI Res. 2016 Dec;6(1):55. doi: 10.1186/s13550-016-0209-4. Epub 2016 Jun 23.
Significant renal mass reduction induced by 5/6 subtotal nephrectomy (Nx) is associated with a chain of events that culminates in hypertension and chronic kidney disease (CKD). Numerous studies have provided evidence for the role of angiotensin (Ang) II type 1 receptor (AT1R) in the promotion and progression of the disease; however, conflicting results were reported on intrarenal AT1R levels in CKD models.
Male Sprague-Dawley rats (n = 26) underwent Nx or sham operations. Animals were scanned at 8-10 weeks post-surgery with PET using the novel AT1R radioligand [(18)F]FPyKYNE-losartan. Radioligand binding was quantified by kidney-to-blood ratio (KBR), standard uptake value (SUV), and distribution volume (DV). After sacrifice, plasma and kidney Ang II levels were measured. Western blot and (125)I-[Sar(1), Ile(8)]Ang II autoradiography were performed to assess AT1R expression.
At 8-10 weeks post-surgery, Nx rats developed hypertension, elevated plasma creatinine levels, left ventricle hypertrophy, increased myocardial blood flow (MBF), and reduced Ang II levels compared to shams. PET measurements displayed significant decrease in KBR (29 %), SUV (24 %), and DV (22 %) induced by Nx (p < 0.05), and these findings were confirmed by in vitro assays.
Reduced renal AT1Rs in hypertensive rats measured with [(18)F]FPyKYNE-losartan PET at 8-10 weeks following Nx support further use of this non-invasive approach in longitudinal studies to better understand the AT1R role in CKD progression.
5/6肾大部切除术（Nx）导致的显著肾质量减少与一系列最终导致高血压和慢性肾脏病（CKD）的事件相关。众多研究已为血管紧张素（Ang）II 1型受体（AT1R）在该疾病的发生和进展中的作用提供了证据；然而，关于CKD模型肾内AT1R水平的报道结果相互矛盾。
雄性Sprague-Dawley大鼠（n = 26）接受Nx手术或假手术。术后8 - 10周用新型AT1R放射性配体[(18)F]FPyKYNE - 氯沙坦通过PET对动物进行扫描。通过肾血比（KBR）、标准摄取值（SUV）和分布容积（DV）对放射性配体结合进行定量。处死后，测量血浆和肾Ang II水平。进行蛋白质免疫印迹和(125)I - [Sar(1), Ile(8)]Ang II放射自显影以评估AT1R表达。
术后8 - 10周，与假手术组相比，Nx大鼠出现高血压、血浆肌酐水平升高、左心室肥厚、心肌血流量（MBF）增加以及Ang II水平降低。PET测量显示Nx诱导的KBR（29%）、SUV（24%）和DV（22%）显著降低（p < 0.05），这些结果通过体外试验得到证实。
Nx术后8 - 10周用[(18)F]FPyKYNE - 氯沙坦PET测量的高血压大鼠肾内AT1R减少，支持在纵向研究中进一步使用这种非侵入性方法，以更好地了解AT1R在CKD进展中的作用。
