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. 2014 Oct;27(10):1285-92.
doi: 10.1093/ajh/hpu048. Epub 2014 Apr 6.

Catheter-based radiorefrequency renal denervation lowers blood pressure in obese hypertensive dogs

Jeffrey R Henegar  1 , Yongxing Zhang  2 , Rita De Rama  2 , Cary Hata  2 , Michael E Hall  3 , John E Hall  4
Affiliations

Catheter-based radiorefrequency renal denervation lowers blood pressure in obese hypertensive dogs

Jeffrey R Henegar et al. Am J Hypertens. 2014 Oct.

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Am J Hypertens. 2015 Jan;28(1):146. doi: 10.1093/ajh/hpu232. Epub 2014 Nov 13. Am J Hypertens. 2015. PMID: 25395612 Free PMC article. No abstract available.

Abstract

Background: Obesity-induced hypertension appears to be due, in part, to increased renal sympathetic activity. Catheter-based renal denervation (RD) has been reported to lower arterial blood pressure (BP) in humans with resistant hypertension, many of whom are obese. This study was performed to assess the impact of radiofrequency-induced RD on renal function, BP, renal norepinephrine (NE), and histology of nerves along the renal artery in obese, hypertensive dogs, an experimental model that closely mimics cardiorenal and metabolic changes in obese hypertensive humans.

Methods: After control measurements of cardiovascular and renal function were obtained in obese dogs fed a high-fat diet, bilateral RD was performed using the St. Jude Medical EnligHTN RD system. After RD, BP was measured continuously for 8 weeks, and glomerular filtration rate (GFR) was measured biweekly for 6 weeks. At the end of the study, renal arteries were collected for histological analysis, and kidneys were obtained for NE measurement.

Results: Eight weeks after RD, systolic BP fell from 157 ± 5 mm Hg pre-RD to 133 ± 3 mm Hg (P < 0.01), and mean arterial pressure decreased by 9 mm Hg compared with pre-RD (P < 0.01). There were no significant changes in GFR. Renal nerve injury was most prevalent 0.28-3.5mm from the renal artery lumen. RD caused injury in 46% of the renal nerves observed and reduced renal tissue NE by 42% (P < 0.01).

Conclusions: Catheter-based RD with the St. Jude Medical EnligHTN system lowers BP in obese dogs without significantly compromising renal function.

Keywords: blood pressure; glomerular filtration; hypertension; obesity; renal denervation..

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Figures

Figure 1.
Figure 1.
Average systolic blood pressure and mean arterial pressure during control (CON) and for 8 weeks after renal denervation in obese dogs (n = 6). Each bar represents the average of 7 days of blood pressure measurements, 18 hours a day, sampled in bursts of 12 seconds each minute at a rate of 500 samples per second. *P < 0.05 vs. CON.
Figure 2.
Figure 2.
Average systolic blood pressure and mean arterial pressure during control and for 8 weeks after renal denervation in obese dogs (n = 6). Each bar represents the average daily blood pressure measurement, 18 hours a day, sampled in bursts of 12 seconds each minute at a rate of 500 samples per second.
Figure 3.
Figure 3.
Glomerular filtration rate (GFR) during the control period (CON) and at weeks 2, 4, and 6 after renal denervation. No significant changes in GFR were observed during the 6 weeks of follow-up measurements after renal denervation.
Figure 4.
Figure 4.
Correlation between systolic blood pressure (SBP) and mean arterial pressure (MAP) and renal tissue norepinephrine (NE) levels.
Figure 5.
Figure 5.
Cumulative percentage of nerves related to the distance (mm) from the renal artery lumen-intima interface. Approximately 85% of renal nerves are within 3.5mm of the renal artery lumen-intima interface.
Figure 6.
Figure 6.
Injury to the renal nerves and artery caused by catheter-based renal denervation. (a) Injured nerve with perineural fibrosis and axon loss (hematoxylin and eosin staining). (b) Injured nerve with inflammation (hematoxylin and eosin staining). (c) Nerve from non–renal denervation animal (hematoxylin and eosin staining). Note thin perineural connective tissue (arrow) and evenly distributed nerve fibers. Scale bars = 50 microns.
Figure 7.
Figure 7.
Injury to the renal nerves and medial fibrosis in the renal artery caused by catheter-based renal denervation. (a) Low magnification showing proximity of nerves to artery lumen, interstitial inflammation (arrows), and injured nerves (arrowheads). Scale bar = 200 microns. (b) Arrow shows medial fibrosis associated with denervation. Trichrome stain. Scale bar = 50 microns.
See this image and copyright information in PMC

Comment in

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