Levels of functional and anatomical reinnervation of afferent and efferent renal nerves in a large animal model following catheter-based renal denervation

It is well established that the renal nerves play an important role in blood pressure regulation. The development of catheter-based renal denervation (RDN) has lead to interest in selective RDN as a treatment for resistant hypertension, but there is little information on the effectiveness of the procedure, the degree of reinnervation and the changes in renal function following denervation. There is also little information on the effects of RDN on the responses to shock. We studied the effects of RDN in sheep using the Symplicity Flex catheter used in humans. In anaesthetised sheep, the RDN procedure consisted of 5–6 two minute radiofrequency ablations, which importantly were performed in the distal portion of the renal arteries where the nerves are closest to the artery. Effective denervation was demonstrated by the absence of renal sympathetic nerve activity, responses to electrical stimulation of the renal nerves and renal anatomical markers of afferent sensory and efferent sympathetic nerves (immunohistochemistry for calcitonin gene related peptide and tyrosine hydroxylase and tissue noradrenaline content). All these changes were reversed by 11 months after RDN, indicating reinnervation of afferent and efferent nerves. Current studies are determining whether RDN has prolonged actions that alter the control of renal blood flow, renin release, and sodium excretion by the reinnervated renal nerves. Further studies indicated greater falls in arterial pressure during septic shock post-RDN. These findings challenge the current presumption that a permanent loss of renal afferent or efferent renal nerves after RDN underlies the long-term reduction in blood pressure in hypertensive patients and indicate that the renal nerves help maintain arterial pressure in states of shock.