Renal Deafferentation Prevents Progression of Hypertension and Changes to Sympathetic Reflexes in a Rabbit Model of Chronic Kidney Disease

Abstract

There is increasing evidence that renal denervation is effective in alleviating hypertension associated with elevation of renal sympathetic nerve activity (RSNA) in chronic kidney disease (CKD), but whether this is due to reduction in renal afferent signaling is unclear. We determined the cardiovascular and sympathetic effects of total renal denervation or afferent renal denervation (topical capsaicin) on CKD induced by glomerular layer lesioning of the left kidney and right nephrectomy in conscious rabbits. CKD increased blood pressure by 18±2 mmHg and plasma creatinine by 40% over 2 to 4 weeks (both P <0.001), while RSNA (43%) and total norepinephrine spillover (28%) were elevated in CKD compared with sham (both P =0.04). After total or afferent renal denervation blood pressure, RSNA and norepinephrine spillover were similar or lower than non-CKD (sham) rabbits. While plasma creatinine in CKD rabbits was not affected by total renal denervation, deafferented rabbits had lower levels ( P =0.017). The greater hypotensive response to pentolinium in CKD was also normalized after total or afferent denervation. Heart rate and RSNA baroreflex gain were similar in all groups. The RSNA response to airjet stress was greater in CKD compared with sham but not after total or afferent renal denervation. By contrast, the sympathetic response to hypoxia was similar in sham and CKD intact or deafferented groups but elevated in total denervated CKD animals. We conclude that the elevated sympathetic activity and blood pressure in this model of CKD is predominantly driven by renal afferents.