What Sets the Long-Term Level of Renal Sympathetic Nerve Activity

Abstract

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...

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