Editorial: Can Renal Denervation Work? Yes, But First One Must Denervate. Lessons from Human Renal Sympathetic Nerve Anatomy

Objectives: This study was designed to observe the efficacy and safety of renal denervation from the inside and outside of renal arteries. Methods: Fourteen beagles were randomly divided into a control group (n = 4) and treatment group (n = 10). One renal artery in every beagle of the treatment group was randomly assigned to an intimal group (10 renal arteries) which underwent percutaneous renal denervation from the inside, and another renal artery was assigned to an adventitial group (10 renal arteries) which underwent renal denervation from the outside by laparotomy. Results: Compared with the intimal group, the renal norepinephrine (NE) concentration in the adventitial group had significantly decreased (p = 0.003) at 3 months postsurgery. Renal artery HE staining showed that the perineurium from the adventitial group appeared thickened. Western blotting showed that renal tissue tyrosine hydroxylase (TH) protein expression in the adventitial group was significantly lower than that in the intimal group (p < 0.01) at 3 months postsurgery. There was a renal artery stenosis and a renal atrophy in the intimal group after 1 month of follow-up. Conclusion: The inhibitory effect on renal sympathetic nerve activity was more effective in the adventitial group than the intimal group, and renal denervation in the former group was safe.

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Renal responses to acute reflex activation of renal sympathetic nerve activity and renal denervation in secondary hypertension

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00217.2007 ◽

2007 ◽

Vol 293 (3) ◽

pp. R1247-R1256 ◽

Cited By ~ 16

Author(s):

Roger G. Evans ◽

Sandra L. Burke ◽

Gavin W. Lambert ◽

Geoffrey A. Head

Keyword(s):

Sympathetic Nerve ◽

Neural Control ◽

Renal Denervation ◽

Sympathetic Nerve Activity ◽

Whole Body ◽

Nerve Activity ◽

Renal Sympathetic Nerve Activity ◽

Renal Sympathetic Nerve ◽

Norepinephrine Spillover ◽

Renal Sympathetic

We tested whether the responsiveness of the kidney to basal renal sympathetic nerve activity (RSNA) or hypoxia-induced reflex increases in RSNA, is enhanced in angiotensin-dependent hypertension in rabbits. Mean arterial pressure, measured in conscious rabbits, was similarly increased (+16 ± 3 mmHg) 4 wk after clipping the left ( n = 6) or right ( n = 5) renal artery or commencing a subcutaneous ANG II infusion ( n = 9) but was not increased after sham surgery ( n = 10). Under pentobarbital sodium anesthesia, reflex increases in RSNA (51 ± 7%) and whole body norepinephrine spillover (90 ± 17%), and the reductions in glomerular filtration rate (−27 ± 5%), urine flow (−43 ± 7%), sodium excretion (−40 ± 7%), and renal cortical perfusion (−7 ± 3%) produced by hypoxia were similar in normotensive and hypertensive groups. Hypoxia-induced increases in renal norepinephrine spillover tended to be less in hypertensive (1.1 ± 0.5 ng/min) than normotensive (3.7 ± 1.2 ng/min) rabbits, but basal overflow of endogenous and exogenous dihydroxyphenolglycol was greater. Renal plasma renin activity (PRA) overflow increased less in hypertensive (22 ± 29 ng/min) than normotensive rabbits (253 ± 88 ng/min) during hypoxia. Acute renal denervation did not alter renal hemodynamics or excretory function but reduced renal PRA overflow. Renal vascular and excretory responses to reflex increases in RSNA induced by hypoxia are relatively normal in angiotensin-dependent hypertension, possibly due to the combined effects of reduced neural norepinephrine release and increased postjunctional reactivity. In contrast, neurally mediated renin release is attenuated. These findings do not support the hypothesis that enhanced neural control of renal function contributes to maintenance of hypertension associated with activation of the renin-angiotensin system.

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Comparison of high-fat style diet-induced dysregulation of baroreflex control of renal sympathetic nerve activity in intact and ovariectomized female rats

Experimental Biology and Medicine ◽

10.1177/1535370220915673 ◽

2020 ◽

Vol 245 (9) ◽

pp. 761-776

Author(s):

Yamuna Sucedaram ◽

Edward James Johns ◽

Ruby Husain ◽

Munavvar Abdul Sattar ◽

Mohammed Abdulla ◽

...

Keyword(s):

Sympathetic Nerve ◽

Renal Denervation ◽

Sympathetic Nerve Activity ◽

Ovarian Hormones ◽

Female Rats ◽

Nerve Activity ◽

Baroreflex Control ◽

Renal Sympathetic Nerve Activity ◽

Renal Sympathetic Nerve ◽

Renal Sympathetic

The present study compared high-fat style diet (HFSD)-induced renal nerve-dependent dysregulation of the baroreflex control of renal sympathetic nerve activity (RSNA) in ovary-intact and ovariectomized (OVX) rats. Female rats received a normal diet (ND) or a HFSD for 10 weeks prior to the acute study. The rats were anesthetized; RSNA and heart rate (HR) were measured. Acute bilateral renal denervation was performed, and baroreflex gain curves were constructed from the baroreflex changes in RSNA to vasopressor and vasodepressor drugs. Cardiopulmonary baroreflex control of RSNA was assessed by acute saline volume expansion (VE). Mean blood pressure was elevated in the OVX-HFSD rats compared to the HFSD group reaching significance on week 6 of the experimental study (P < 0.01). Adiposity index and creatinine clearance were significantly greater in all HFSD rats compared to their ND counterparts. Fractional excretion of sodium rose initially in all HFSD rats but was normalized towards the end of the study although absolute sodium excretion remained high. In the acute study, baroreflex gain curve sensitivity (A2) of RSNA was similarly decreased in both the HFSD and OVX-HFSD rats by 88% (P < 0.005) and 94% (P < 0.001) respectively compared to their control counterparts, but was normalized following bilateral renal denervation. VE-reduced RSNA in ND and OVX-ND rats by 55% and 52% (both P < 0.001) respectively, but did not alter RSNA in both HFSD and OVX-HFSD female rats. Following bilateral renal denervation, HFSD and OVX-HFSD rats exhibited 37% (P < 0.01) and 24% (P < 0.01) reduction in RSNA respectively. These findings demonstrate that although obesity-induced impairment of baroreflex control of RSNA occurred similarly in HFSD and OVX-HFSD rats, mean blood pressure was increased only in the ovarian hormones deprived-group suggesting that ovarian hormones could have modulatory role on other mechanisms that regulate blood pressure in female obesity. Impact statement Over activation of renal sensory nerve in obesity blunts the normal regulation of renal sympathetic nerve activity. To date, there is no investigation that has been carried out on baroreflex regulation of renal sympathetic nerve activity in obese ovarian hormones deprived rat model, and the effect of renal denervation on the baroreflex regulation of renal sympathetic nerve activity. Thus, we investigated the role of renal innervation on baroreflex regulation of renal sympathetic nerve activity in obese intact and ovariectomized female rats. Our data demonstrated that in obese states, the impaired baroreflex control is indistinguishable between ovarian hormones deprived and non-deprived states. This study will be of substantial interest to researchers working on the impact of diet-induced hypertension in pre- and postmenopausal women. This study provides insight into health risks amongst obese women regardless of their ovarian hormonal status and may be integrated in preventive health strategies.

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TCT CONNECT-10 Anatomy of Human Accessory Renal Artery Peri-Arterial Renal Sympathetic Nerve for Renal Denervation

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2020.09.024 ◽

2020 ◽

Vol 76 (17) ◽

pp. B4-B5

Author(s):

Yu Sato ◽

Rika Kawakami ◽

Hiroyuki Jinnouchi ◽

Atsushi Sakamoto ◽

Anne Cornelissen ◽

...

Keyword(s):

Renal Artery ◽

Sympathetic Nerve ◽

Renal Denervation ◽

Accessory Renal Artery ◽

Renal Sympathetic Nerve ◽

Renal Sympathetic

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Effects of sympathetic nerves and angiotensin II on renal sodium and water handling in rats with common bile duct ligature

AJP Renal Physiology ◽

10.1152/ajprenal.00069.2003 ◽

2005 ◽

Vol 288 (6) ◽

pp. F1267-F1275 ◽

Cited By ~ 15

Author(s):

Roland Veelken ◽

Karl F. Hilgers ◽

Markus Porst ◽

Holger Krause ◽

Andrea Hartner ◽

...

Keyword(s):

Angiotensin Ii ◽

Sympathetic Nerve ◽

Renal Denervation ◽

Sympathetic Nerve Activity ◽

Nerve Activity ◽

Renal Sympathetic Nerve Activity ◽

Renal Sympathetic Nerve ◽

Volume Load ◽

Volume Retention ◽

Renal Sympathetic

We tested the hypothesis that angiotensin II is likely to be mandatory for the neurogenic sodium and volume retention in cirrhotic rats with common bile duct ligature (BDL) following an acute volume load. To assess the neural control of volume homeostasis, 21 days after common BDL rats underwent volume expansion (0.9% NaCL; 10% body wt over 30 min) to decrease renal sympathetic nerve activity. Untreated animals, rats with renal denervation or pretreated with a nonhypotensive dose of an angiotensin II type 1 receptor antagonist were studied. The renal renin-angiotensin system was assessed by immunohistochemistry and RT-PCR. Rats with BDL excreted only 71 ± 4% of the administered volume load. In cirrhotic rats pretreated with an angiotensin II AT1 inhibitor or after renal denervation, these values ranged significantly higher from 98 to 103% ( P < 0.05 for all comparisons). Renal sympathetic nerve activity decreases by volume expansion were impaired in BDL rats ( P < 0.05) but unaffected by angiotensin II receptor inhibition. In kidneys of BDL animals, renin mRNA was increased, and immunohistochemistry revealed increased staining for peritubular angiotensin II. Renal denervation in BDL animals reduced renin expression within 5 days to control levels. In conclusion, the impaired excretion of an acute volume load in rats with liver cirrhosis is due to effects of an increased renal sympathetic nerve activity that are likely to be dependent on intrarenal angiotensin II and renin. We speculate that similar changes may contribute to long-term volume retention in liver cirrhosis.

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Synergy of pulmonary vein isolation and catheter renal denervation in atrial fibrillation complicated with uncontrolled hypertension: Mapping the renal sympathetic nerve and pulmonary vein (the pulmonary vein isolation plus renal denervation strategy)?

Journal of Cardiovascular Electrophysiology ◽

10.1111/jce.13858 ◽

2019 ◽

Vol 30 (5) ◽

pp. 658-667 ◽

Cited By ~ 2

Author(s):

Shaojie Chen ◽

Marcio G. Kiuchi ◽

Yuehui Yin ◽

Shaowen Liu ◽

Alexandra Schratter ◽

...

Keyword(s):

Atrial Fibrillation ◽

Pulmonary Vein ◽

Pulmonary Vein Isolation ◽

Sympathetic Nerve ◽

Renal Denervation ◽

Uncontrolled Hypertension ◽

Renal Sympathetic Nerve ◽

Renal Sympathetic

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Renal nerve activity and renal function during environmental stress in DOCA-NaCl rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1986.251.2.r289 ◽

1986 ◽

Vol 251 (2) ◽

pp. R289-R294 ◽

Cited By ~ 3

Author(s):

J. P. Koepke ◽

S. Jones ◽

G. F. DiBona

Keyword(s):

Mean Arterial Pressure ◽

Arterial Pressure ◽

Sympathetic Nerve ◽

Renal Denervation ◽

Sympathetic Nerve Activity ◽

Hypertensive Rats ◽

Nerve Activity ◽

Renal Sympathetic Nerve Activity ◽

Renal Sympathetic Nerve ◽

Renal Sympathetic

The effects of a stressful environmental stimulus (air stress) on mean arterial pressure, heart rate, renal sympathetic nerve activity, and renal function were studied in conscious deoxycorticosterone acetate-sodium chloride (DOCA-NaCl) hypertensive rats, sham DOCA-NaCl normotensive rats, and DOCA-NaCl rats with renal denervation. In conscious DOCA-NaCl hypertensive rats, air stress decreased urine flow rate [36% from 17.9 +/- 3.0 microliter X min-1 X 100 g body wt-1 (BW)], urinary sodium excretion (39% from 3.1 +/- 0.5 microeq X min-1 X 100 g BW-1), fractional water excretion (24% from 4.72 +/- 1.00%), and fractional sodium excretion (28% from 5.72 +/- 1.08%) and increased renal sympathetic nerve activity (94% from 8.3 +/- 0.6 integrator resets/min), but no changes occurred in glomerular filtration rate (-15% from 0.40 +/- 0.06 ml X min-1 X 100 g BW-1) or effective renal plasma flow (-7% from 2.50 +/- 0.53 ml X min-1 X 100 g BW-1). Air stress had no effect on these measures in conscious sham DOCA-NaCl normotensive rats or DOCA-NaCl rats with renal denervation. Mean arterial pressure and heart rate were unaffected by air stress in these three groups. Renal denervation lowered base-line mean arterial pressure in DOCA-NaCl rats. Thus DOCA-NaCl hypertensive rats respond to environmental stress with increased renal sympathetic nerve activity and, consequently, antidiuresis and antinatriuresis.

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Chronic renal denervation increases renal tubular response to P2X receptor agonists in rats: implication for renal sympathetic nerve ablation

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfs087 ◽

2012 ◽

Vol 27 (9) ◽

pp. 3443-3448 ◽

Cited By ~ 10

Author(s):

R. Kowalski ◽

E. Kreft ◽

M. Kasztan ◽

M. Jankowski ◽

M. Szczepanska-Konkel

Keyword(s):

Sympathetic Nerve ◽

Renal Denervation ◽

P2x Receptor ◽

Receptor Agonists ◽

Renal Sympathetic Nerve ◽

Renal Tubular ◽

Renal Sympathetic

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Effect of renal denervation on dynamic autoregulation of renal blood flow

AJP Renal Physiology ◽

10.1152/ajprenal.00010.2004 ◽

2004 ◽

Vol 286 (6) ◽

pp. F1209-F1218 ◽

Cited By ~ 43

Author(s):

Gerald F. DiBona ◽

Linda L. Sawin

Keyword(s):

Blood Flow ◽

Renal Blood Flow ◽

Sympathetic Nerve ◽

Renal Denervation ◽

Sympathetic Nerve Activity ◽

Nerve Activity ◽

Renal Sympathetic Nerve Activity ◽

Spontaneously Hypertensive ◽

Renal Sympathetic Nerve ◽

Renal Sympathetic

Vasoconstrictor intensities of renal sympathetic nerve stimulation elevate the renal arterial pressure threshold for steady-state stepwise autoregulation of renal blood flow. This study examined the tonic effect of basal renal sympathetic nerve activity on dynamic autoregulation of renal blood flow in rats with normal (Sprague-Dawley and Wistar-Kyoto) and increased levels of renal sympathetic nerve activity (congestive heart failure and spontaneously hypertensive rats). Steady-state values of arterial pressure and renal blood flow before and after acute renal denervation were subjected to transfer function analysis. Renal denervation increased basal renal blood flow in congestive heart failure (+35 ± 3%) and spontaneously hypertensive rats (+21 ± 3%) but not in Sprague-Dawley and Wistar-Kyoto rats. Renal denervation significantly decreased transfer function gain (i.e., improved autoregulation of renal blood flow) and increased coherence only in spontaneously hypertensive rats. Thus vasoconstrictor intensities of renal sympathetic nerve activity impaired the dynamic autoregulatory adjustments of the renal vasculature to oscillations in arterial pressure. Renal denervation increased renal blood flow variability in spontaneously hypertensive rats and congestive heart failure rats. The contribution of vasoconstrictor intensities of basal renal sympathetic nerve activity to limiting renal blood flow variability may be important in the stabilization of glomerular filtration rate.

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