Abstract-Increasing evidence suggests elevated sympathetic outflow may be important in the genesis of hypertension. It is thought that peripheral angiotensin II, in addition to its pressor actions, may act centrally to increase sympathetic nerve activity (SNA). Without direct long-term recordings of SNA, testing the involvement of neural mechanisms in angiotensin II-induced increases in arterial pressure is difficult. Using a novel telemetry-based implantable amplifier, we made continuous recordings of renal SNA (RSNA) before, during, and after 1 week of angiotensin II-based hypertension in rabbits living in their home cages. Angiotensin II infusion (50 ng · kg Ϫ1 · min Ϫ1) caused a sustained increase in arterial pressure (18Ϯ3 mm Hg). There was a sustained decrease in RSNA from 18Ϯ2 normalized units (n.u.) before angiotensin II to 8Ϯ2 n.u. on day 2 and 9Ϯ2 n.u. on day 7 of the angiotensin II infusion (PϽ0.01) before recovering to 17Ϯ2 n.u. after ceasing angiotensin II. Analysis of the baroreflex response showed that although angiotensin II-induced hypertension led to resetting of the relationship between mean arterial pressure (MAP) and heart rate, there was no evidence of resetting of the MAP-RSNA relationship. We propose that the lack of resetting of the MAP-RSNA curve, with the resting point lying near the lower plateau, suggests the sustained decrease in RSNA during angiotensin II is baroreflex mediated. These results suggest that baroreflex control of RSNA and thus renal function is likely to play a significant role in the control of arterial pressure not only in the short term but also in the long term. Key Words: rabbits Ⅲ telemetry Ⅲ angiotensin II Ⅲ baroreflex Ⅲ sympathetic nerve activity S everal previous studies indicate that the sympathetic nervous system plays a critical role in the development of hypertension. In young or borderline hypertensive subjects, it is clear that plasma catecholamines are elevated 1-3 and muscle sympathetic activity is increased. 4,5 Importantly, it seems that rather than generalized overactivity of the sympathetic nervous system occurring, it is specifically increased renal sympathetic nerve activity (RSNA), resulting in diminished renal function, that is important. In young borderline hypertensive patients, noradrenaline spillover from the kidney is particularly elevated. 6,7 Animal models have identified that the onset of hypertension may be delayed or the magnitude of the arterial pressure elevation may be reduced by chronic renal denervation. 8 -12 Other studies have used longterm infusions of norepinephrine directly into the renal artery to mimic increased RSNA and observed the retention of sodium and water and sustained increases in arterial pressure. [13][14][15] These results have been interpreted to suggest that an integral relationship exists between functional sympathetic outflow to the kidneys and the development of hypertension.Although much progress has been made in recent years on the central nervous system pathways involved in regulating sympathetic acti...

T here is extensive evidence that renal afferent and efferent nerves play a critical role in the control of renal function and in setting the level of arterial blood pressure.1 This includes the findings that in experimental and human hypertension there are increases in renal sympathetic nerve activity (RSNA) and renal norepinephrine spillover, respectively. In addition, surgical renal denervation (RDN) reduces blood pressure in hypertensive animals and patients, 1-4 although in patients this was associated with several side effects. 4 The development of catheter-based radiofrequency RDN has resulted in a resurgence of interest in RDN as a treatment for resistant hypertensive patients. Initial trials demonstrated reductions in office systolic blood pressure 5,6 and in the 36-month follow-up from the first trial 93% of patients showed reductions in office systolic blood pressure of ≥10 mm Hg after RDN. 7 In contrast, the recent Symplicity HTN-3 trial did not demonstrate reductions in systolic blood pressure beyond that observed in sham control patients 6 months after RDN, 8 although there is still debate on factors that may have led to the lack of effect, such as procedural and population variability.It would be expected that destruction of the renal nerves reduces blood pressure because the efferent renal nerves play a major role in stimulating renin release, causing renal vasoconstriction and inducing sodium retention.1 It is also plausible that in hypertension, increased afferent renal nerve activity may cause a reflex increase in sympathetic outflow and worsening hypertension.9,10 Such actions are supported by findings that in some hypertensive patients, catheter-based RDN reduced the level of muscle SNA 11,12 and plasma norepinephrine. 13 Despite these proposed mechanisms, it is unknown how Abstract-Previous studies indicate that catheter-based renal denervation reduces blood pressure and renal norepinephrine spillover in human resistant hypertension. The effects of this procedure on afferent sensory and efferent sympathetic renal nerves, and the subsequent degree of reinnervation, have not been investigated. We therefore examined the level of functional and anatomic reinnervation at 5.5 and 11 months after renal denervation using the Symplicity Flex catheter. In normotensive anesthetized sheep (n=6), electric stimulation of intact renal nerves increased arterial pressure from 99±3 to 107±3 mm Hg (afferent response) and reduced renal blood flow from 198±16 to 85±20 mL/min (efferent response). In a further group (n=6), immediately after denervation, renal sympathetic nerve activity was absent and the responses to electric stimulation were abolished. At 11 months after denervation (n=5), renal sympathetic nerve activity and the responses to electric stimulation were at normal levels. Immunohistochemical staining for renal efferent (tyrosine hydroxylase) and renal afferent nerves (calcitonin gene-related peptide), as well as renal norepinephrine levels, was normal 11 months after denervation. Findings at 5.5...