Potential Renoprotective Effects of Chronic Remote Ischemic Conditioning in a Rodent Model of Sleep Apnea

Abstract

Sleep apnea (SA) is a chronic condition characterized by recurrent cessation of airflow during sleep. Episodes of SA lead to hemodynamic perturbations, neurohormonal activation, and repeated cycles of hypoxia/reoxygenation. SA is independently associated with chronic kidney disease however the underlying mechanisms are incompletely understood. It is theorized that oxidative stress, inflammation, and activation of pro‐fibrotic signaling in the kidney may underlie this association. Remote ischemic conditioning (RIC) is the application of circulatory occlusion to an extremity to induce transient ischemia. This ischemia stimulates a cascade of signals which spread throughout the body via neural and humoral pathways and stimulates adaptive changes in distant organs that aid in resisting future ischemic insults. There is evidence that remote ischemic conditioning has protective effects in the kidney in acute applications, however it has never been investigated in the context of treatment for chronic disease. We hypothesized that application of RIC in a rodent model of SA (chronic intermittent hypoxia, CIH) would have beneficial effects on regulation of renal hemodynamics and would attenuate inflammation, oxidative stress, and pro‐fibrotic signaling. Adult male Sprague Dawley rats were exposed to CIH or sham for 14 days; two sub‐groups (n=6 per group) received RIC every 48 hours over the final 7 days. Renal perfusion and PO2 were measured at baseline and in response to hypoxia. Cortical tissue was assessed for gene expression related to inflammation, oxidative stress, and fibrosis using qRT‐PCR. CIH resulted in baseline reductions in renal blood flow and PO2 relative to sham in addition to greater hypoxia‐evoked reductions in these measures(p>0.05). No differences were observed in renal blood flow/perfusion or PO2 between RIC‐AIR and RIC‐CIH groups (p>0.05). Cortical expression of IL‐6, IL‐1β, CuZn‐SOD, and Collagen III were increased in CIH vs. sham (p<0.05), whereas no differences in expression where observed between RIC‐AIR and RIC‐CIH groups (p>0.05). These results suggest RIC may confer a salutary effect on regulation of renal hemodynamics and biochemical changes associated with exposure to CIH.