Department of Cell Biology and Physiology, University of New Mexico , Albuquerque, New Mexico.
Am J Physiol Renal Physiol. 2018 Oct 1;315(4):F927-F941. doi: 10.1152/ajprenal.00420.2017. Epub 2018 Jun 13.
Kidney injury and sleep apnea (SA) are independent risk factors for hypertension. Exposing rats to intermittent hypoxia (IH) to simulate SA increases blood pressure whereas adenine feeding causes persistent kidney damage to model chronic kidney disease (CKD). We hypothesized that exposing CKD rats to IH would exacerbate the development of hypertension and renal failure. Male Sprague-Dawley rats were fed a 0.2% adenine diet or control diet (Control) until blood urea nitrogen was >120 mg/dl in adenine-fed rats (14 ± 4 days, mean ± SE). After 2 wk of recovery on normal chow, rats were exposed to IH (20 exposures/h of 5% O-5% CO 7 h/day) or control conditions (Air) for 6 wk. Mean arterial pressure (MAP) was monitored with telemeters, and plasma and urine samples were collected weekly to calculate creatinine clearance as an index of glomerular filtration rate (GFR). Prior to IH, adenine-fed rats had higher blood pressure than rats on control diet. IH treatment increased MAP in both groups, and after 6 wk, MAP levels in the CKD/IH rats were greater than those in the CKD/Air and Control/IH rats. MAP levels in the Control/Air rats were lower than those in the other three groups. Kidney histology revealed crystalline deposits, tubule dilation, and interstitial fibrosis in both CKD groups. IH caused no additional kidney damage. Plasma creatinine was similarly increased in both CKD groups throughout whereas IH alone increased plasma creatinine. IH increases blood pressure further in CKD rats without augmenting declines in GFR but appears to impair GFR in healthy rats. We speculate that treating SA might decrease hypertension development in CKD patients and protect renal function in SA patients.
肾脏损伤和睡眠呼吸暂停（SA）是高血压的独立危险因素。通过间歇性低氧（IH）暴露大鼠来模拟 SA 会导致血压升高，而给予腺嘌呤喂养则会导致持续性肾损伤以模拟慢性肾病（CKD）。我们假设将 CKD 大鼠暴露于 IH 会加重高血压和肾功能衰竭的发展。雄性 Sprague-Dawley 大鼠喂食 0.2%腺嘌呤饮食或对照饮食（对照），直到腺嘌呤喂养大鼠的血尿素氮>120mg/dl（14±4 天，均值±SE）。在正常饲料上恢复 2 周后，大鼠暴露于 IH（5%O-5%CO 20 次/小时，每天 7 小时）或对照条件（空气）6 周。使用遥测仪监测平均动脉压（MAP），每周收集血浆和尿液样本以计算肌酐清除率作为肾小球滤过率（GFR）的指标。在 IH 之前，腺嘌呤喂养的大鼠的血压高于对照饮食的大鼠。IH 处理增加了两组大鼠的 MAP，并且在 6 周后，CKD/IH 大鼠的 MAP 水平高于 CKD/Air 和 Control/IH 大鼠。Control/Air 大鼠的 MAP 水平低于其他三组。肾组织学显示两组 CKD 大鼠均有结晶沉积、小管扩张和间质纤维化。IH 没有引起额外的肾脏损伤。整个 CKD 两组的血浆肌酐均类似增加，而 IH 单独增加了血浆肌酐。IH 进一步增加了 CKD 大鼠的血压，而没有增加 GFR 的下降，但似乎会损害健康大鼠的 GFR。我们推测，治疗 SA 可能会降低 CKD 患者高血压的发展并保护 SA 患者的肾功能。
