Sympathoinhibitory Effect of Radiofrequency Renal Denervation in Spontaneously Hypertensive Rats With Established Hypertension

Am J Hypertens. 2016 Dec 1;29(12):1394-1401. doi: 10.1093/ajh/hpw089.

Abstract

Background: Radiofrequency ablation of the renal arteries (RF-ABL) has been shown to decrease blood pressure (BP) in drug-resistant hypertensive patients who receive antihypertensive drug therapy. However, there remain questions regarding how RF-ABL influences BP independent of drug therapy and whether complete renal denervation is necessary to maximally lower BP. To study these questions, we examined the cardiovascular, sympathetic, and renal effects produced by RF-ABL of the proximal renal arteries in spontaneously hypertensive rats (SHR) with established hypertension.

Methods: SHR were instrumented (telemetry) for measurement of systolic/diastolic BP (SBP/DBP). Rats then underwent Sham-ABL or RF-ABL adjacent to the renal ostium and BP was recorded for 8 weeks. Changes in sympathetic activity, 24-hour water/sodium excretion, and levels of urinary angiotensinogen (AGT), plasma renin activity, and kidney renin content (KRC) were measured in SHR.

Results: Compared with Sham-ABL, RF-ABL produced a sustained decrease in BP. At 8 weeks, SBP/DBP was 171±6/115±3 and 183±4/129±3mm Hg for RF-ABL and Sham-ABL SHR, respectively. Correlating with the reduction in BP, RF-ABL significantly decreased the low frequency/total and low frequency/high frequency of BP variability and attenuated the hypotensive response to chlorisondamine. Kidney norepinephrine levels were markedly decreased at 8 weeks in RF-ABL vs. Sham-ABL SHR. There were no group differences in 24-hour sodium/water excretion or urinary AGT excretion rate (6 weeks) or plasma renin activity or KRC (8 weeks). In other studies, concurrent RF-ABL plus surgical denervation initially decreased BP to a greater level than RF-ABL alone, but thereafter the reduction in BP between groups was not different.

Conclusions: In hypertensive SHR, bilateral RF-ABL of the proximal renal arteries produced a sustained decease in sympathetic activity and BP without changes in sodium/water excretion or activity of the systemic/renal renin-angiotensin system.

Keywords: blood pressure; hypertension; kidney norepinephrine; radiofrequency renal nerve ablation; renal denervation; renal nerves; spontaneously hypertensive rats; sympathetic nerve activity; urinary sodium excretion..

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensinogen / urine
  • Animals
  • Blood Pressure
  • Catheter Ablation*
  • Disease Models, Animal
  • Hypertension / physiopathology
  • Hypertension / surgery*
  • Kidney / blood supply*
  • Male
  • Natriuresis
  • Neural Inhibition*
  • Norepinephrine / metabolism
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Renal Artery / innervation*
  • Renin / blood
  • Renin-Angiotensin System
  • Sympathectomy / methods*
  • Sympathetic Nervous System / metabolism
  • Sympathetic Nervous System / physiopathology
  • Sympathetic Nervous System / surgery*
  • Time Factors
  • Urination

Substances

  • Agt protein, rat
  • Angiotensinogen
  • Renin
  • Norepinephrine