Renal sympathetic denervation inhibits postapneic blood pressure rises and renal hypoperfusion in a pig model for obstructive sleep apnea

Abstract

Purpose: Obstructive Sleep Apnea (OSA) is associated with hypertension and the progression of Chronic kidney Disease (CKD). Renal sympathetic innervation contributes to either condition. Methods: We investigated the effect of Renal sympathetic Denervation (RDN) on Blood Pressure (BP), renal perfusion and neurohumoral responses during and after repetitive obstructive apneas in a pig model for OSA. BP, femoral artery and renal artery flow were measured in 34 spontaneously breathing urethane-chloralose anesthetized pigs. The effect of RDN (n=14) and irbesartan (n=3) was investigated. Repetitive tracheal occlusions for 2 min with applied negative tracheal pressure at -80 mbar were performed over 4 hours. Results: Spontaneous breathing attempts during tracheal occlusion caused an intra-apneic oscillating breathing-synchronous pattern of renal flow. Renal flow oscillations were more than twofold higher with a gain between renal flow and BP of 2.9%/mmHg compared with femoral flow that almost showed changes proportional to the BP-alterations (1.3%/mmHg; p<0.0001). A marked post-apneic BP-rise from 102+3 to 172+8mmHg (p<0.00001) was associated with renal hypoperfusion (from 190+24 to 70+20ml/min, p<0.00001) occurring after application of NTP. RDN, but not irbesartan, inhibited post-apneic BP rises and renal hypoperfusion and attenuated increased plasma renin activity and aldosterone concentration induced by repetitive tracheal occlusions. Additionally, increased urinary protein/creatinine-ratio was significantly reduced by RDN, while intra-apneic hemodynamic changes or blood gases were not significantly modified by RDN. Conclusions: RDN inhibits post-apneic BP-rises and renal hypoperfusion and attenuates neurohumoral responses and increased protein/creatinine-ratio induced by repetitive obstructive apneas. RDN may, therefore, provide beneficial effects in patients with OSA and hypertension.