Renal and cardiac effects of the PDE9 inhibitor BAY 73-6691 in 5/6 nephrectomized rats.

We examined the effects of the PDE9 inhibitor BAY 73-6691 on the kidney and heart for the first time in a 5/6 nephrectomy animal model using BAY 73-6691 dosages known to be effective in other rat disease models. We did not observe any relevant effects of the PDE9 inhibitor BAY 73-6691 on renal function, renal histology, and renal disease-related pathways and gene expression in 5/6 nephrectomy rats. In addition, the effects of the PDE9 inhibitor BAY 73-6691 on the heart of 5/6 nephrectomy rats were mild. Except for cardiomyocyte size, BAY 73-6691 had no effect on other cardiac histological parameters, cardiac function, and disease-related genes and pathways.

本研究首次采用BAY 73-6691 PDE9抑制剂在5/6肾切除动物模型中考察其对肾脏和心脏的影响，该剂量在其他大鼠疾病模型中已知具有疗效。研究未观察到BAY 73-6691 PDE9抑制剂对5/6肾切除大鼠的肾功能、肾脏组织学以及与肾脏疾病相关的通路和基因表达产生任何显著影响。此外，BAY 73-6691 PDE9抑制剂对5/6肾切除大鼠心脏的影响轻微。除心肌细胞大小外，BAY 73-6691对其他心脏组织学参数、心脏功能以及与疾病相关的基因和通路无显著影响。