Department of Physiology, School of Medicine, College of Medicine and Health, University College Cork, Cork, Ireland.
Am J Physiol Renal Physiol. 2021 Jan 1;320(1):F1-F16. doi: 10.1152/ajprenal.00377.2020. Epub 2020 Nov 9.
We examined the effects of exposure to chronic intermittent hypoxia (CIH) on baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory responses to volume expansion (VE) before and after intrarenal transient receptor potential vanilloid 1 (TRPV1) blockade by capsaizepine (CPZ). Male Wistar rats were exposed to 96 cycles of hypoxia per day for 14 days (CIH) or normoxia. Urine flow and absolute Na excretion during VE were less in CIH-exposed rats, but the progressive decrease in RSNA during VE was preserved. Assessment of the high-pressure baroreflex revealed an increase in the operating and response range of RSNA and decreased slope in CIH-exposed rats with substantial hypertension [+19 mmHg basal mean arterial pressure (MAP)] but not in a second cohort with modest hypertension (+12 mmHg). Intrarenal CPZ caused diuresis, natriuresis, and a reduction in MAP in sham-exposed (sham) and CIH-exposed rats. After intrarenal CPZ, diuretic and natriuretic responses to VE in CIH-exposed rats were equivalent to those of sham rats. TRPV1 expression in the renal pelvic wall was similar in both experimental groups. Exposure to CIH did not elicit glomerular hypertrophy, renal inflammation, or oxidative stress. We conclude that exposure to CIH ) does not impair the low-pressure baroreflex control of RSNA; ) has modest effects on the high-pressure baroreflex control of RSNA, most likely indirectly due to hypertension; ) can elicit hypertension in the absence of kidney injury; and ) impairs diuretic and natriuretic responses to fluid overload. Our results suggest that exposure to CIH causes renal dysfunction, which may be relevant to obstructive sleep apnea.
我们研究了慢性间歇性低氧（CIH）暴露对肾交感神经活动（RSNA）的压力反射控制以及肾对容量扩张（VE）的排泄反应的影响，在此之前，通过辣椒素（CPZ）阻断肾瞬时受体电位香草酸 1（TRPV1）。雄性 Wistar 大鼠每天暴露于 96 个低氧周期（CIH）或常氧 14 天。VE 期间，CIH 暴露大鼠的尿量和绝对 Na 排泄减少，但 VE 期间 RSNA 的逐渐减少得到保留。评估高压压力反射发现，CIH 暴露大鼠的 RSNA 操作和反应范围增加，斜率降低，同时伴有明显的高血压[基础平均动脉压（MAP）升高 19mmHg]，但在另一个高血压程度较轻（+12mmHg）的大鼠中则没有。肾内 CPZ 引起假手术（sham）和 CIH 暴露大鼠的利尿、排钠和 MAP 降低。肾内 CPZ 后，CIH 暴露大鼠的 VE 利尿和排钠反应与 sham 大鼠相当。两组实验中，肾集合管壁的 TRPV1 表达相似。CIH 暴露并未引起肾小球肥大、肾炎症或氧化应激。我们得出结论，CIH 暴露：）不会损害 RSNA 的低压压力反射控制；）对 RSNA 的高压压力反射控制有适度影响，很可能是由于高血压间接引起的；）在没有肾脏损伤的情况下也能引起高血压；并）损害对液体超负荷的利尿和排钠反应。我们的结果表明，CIH 暴露会导致肾功能障碍，这可能与阻塞性睡眠呼吸暂停有关。
