Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Drug Discovery Center, Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Drug Discovery Center, Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Biochem Pharmacol. 2023 Apr;210:115438. doi: 10.1016/j.bcp.2023.115438. Epub 2023 Jan 27.
The incidence of ureter obstruction is increasing and patients recovering from this kidney injury often progress to chronic kidney injury. There is evidence that a long-term consequence of recovery from ureter obstruction is an increased risk for salt-sensitive hypertension. A reversal unilateral ureteral obstruction (RUUO) model was used to study long-term kidney injury and salt-sensitive hypertension. In this model, we removed the ureteral obstruction at day 10 in mice. Mice were divided into four groups: (1) normal salt diet, (2) high salt diet, (3) RUUO normal salt diet, and (4) RUUO high salt diet. At day 10, the mice were fed a normal or high salt diet for 4 weeks. Blood pressure was measured, and urine and kidney tissue collected. There was a progressive increase in blood pressure in the RUUO high salt diet group. RUUO high salt group had decreased sodium excretion and glomerular injury. Renal epithelial cell injury was evident in RUUO normal and high salt mice as assessed by neutrophil gelatinase-associated lipocalin (NGAL). Kidney inflammation in the RUUO high salt group involved an increase in F4/80 positive macrophages; however, CD3+ positive T cells were not changed. Importantly, RUUO normal and high salt mice had decreased vascular density. RUUO was also associated with renal fibrosis that was further elevated in RUUO mice fed a high salt diet. Overall, these findings demonstrate long-term renal tubular injury, inflammation, decreased vascular density, and renal fibrosis following reversal of unilateral ureter obstruction that could contribute to impaired sodium excretion and salt-sensitive hypertension.
输尿管梗阻的发病率正在增加，从这种肾损伤中恢复的患者常进展为慢性肾损伤。有证据表明，输尿管梗阻恢复的长期后果是盐敏感性高血压的风险增加。采用单侧输尿管梗阻（UUO）逆转模型来研究长期肾损伤和盐敏感性高血压。在该模型中，我们在第 10 天去除输尿管梗阻。将小鼠分为四组：（1）正常盐饮食组；（2）高盐饮食组；（3）UUO 正常盐饮食组；（4）UUO 高盐饮食组。在第 10 天，小鼠开始分别接受正常盐或高盐饮食 4 周。测量血压，收集尿液和肾组织。UUO 高盐饮食组的血压逐渐升高。与 UUO 正常盐饮食组相比，UUO 高盐饮食组的钠排泄减少，肾小球损伤加重。用中性粒细胞明胶酶相关脂质运载蛋白（NGAL）评估，UUO 正常盐和高盐饮食组的肾上皮细胞损伤明显。在 UUO 高盐饮食组中，肾脏炎症涉及 F4/80 阳性巨噬细胞增加，而 CD3+阳性 T 细胞没有变化。重要的是，UUO 正常盐和高盐饮食组的血管密度降低。UUO 还与肾纤维化有关，在 UUO 高盐饮食组中，肾纤维化进一步加重。总之，这些发现表明，单侧输尿管梗阻逆转后可长期导致肾小管损伤、炎症、血管密度降低和肾纤维化，这可能导致钠排泄减少和盐敏感性高血压。
