Blood pressure response to renal denervation is correlated with baseline blood pressure variability

Persu, Alexandre; Gordin, Daniel; Jacobs, Lotte; Thijs, Lutgarde; Bots, Michiel L.; Spiering, Wilko; Miroslawska, Atena; Spaak, Jonas; Rosa, Ján; Jong, Mark R. de; Berra, E.; Elmula, Fadl Elmula M. Fadl; Wuerzner, Grégoire; Taylor, Alison; Olszanecka, Agnieszka; Czarnecka, Danuta; Mark, Patrick B.; Burnier, Michel; Renkin, Jean; Kjeldsen, Sverre E.; Widimský, Jiří; Elvan, Arif; Kahan, Thomas; Steigen, Terje K.; Blankestijn, Peter J.; Tikkanen, Ilkka; Staessen, Jan A.

doi:10.1097/hjh.0000000000001582

Cited by 20 publications

(13 citation statements)

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“…Furthermore, the significant reduction in the MESOR and amplitude of mean arterial pressure diurnal rhythm may be indicative of a suppressed sympathetic tone (17), since sympathetic activity is highest during the active phase. A similar mechanism was posited in the recent clinical studies from Persu et al (41) and Ewen et al (14) in which reduced blood pressure variability following catheter-based RDNx in hypertensive patients was hypothesized to be a result of sympathetic suppression. Our data support this hypothesis in that sympathetic tone assessed by ganglionic blockade was reduced by TRDNx and ARDNx.…”

Section: Discussionsupporting

confidence: 56%

Targeted afferent renal denervation reduces arterial pressure but not renal inflammation in established DOCA-salt hypertension in the rat

Banek

Gauthier

Baumann

et al. 2018

American Journal of Physiology-Regulatory, Integrative and Comp

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Recent preclinical studies show renal denervation (RDNx) may be an effective treatment for hypertension; however, the mechanism remains unknown. We have recently reported total RDNx (TRDNx) and afferent-selective RDNx (ARDNx) similarly attenuated the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Whereas TRDNx abolished renal inflammation, ARDNx had a minimal effect despite an identical antihypertensive effect. Although this study established that ARDNx attenuates the development of DOCA-salt hypertension, it is unknown whether this mechanism remains operative once hypertension is established. The current study tested the hypothesis that TRDNx and ARDNx would similarly decrease mean arterial pressure (MAP) in the DOCA-salt hypertensive rat, and only TRDNx would mitigate renal inflammation. After 21 days of DOCA-salt treatment, male Sprague-Dawley rats underwent TRDNx ( n = 16), ARDNx ( n = 16), or Sham ( n = 14) treatment and were monitored for 14 days. Compared with baseline, TRDNx and ARDNx decreased MAP similarly (TRDNx -14 ± 4 and ARDNx -15 ± 6 mmHg). After analysis of diurnal rhythm, rhythm-adjusted mean and amplitude of night/day cycle were also reduced in TRDNx and ARDNx groups compared with Sham. Notably, no change in renal inflammation, injury, or function was detected with either treatment. We conclude from these findings that: 1) RDNx mitigates established DOCA-salt hypertension; 2) the MAP responses to RDNx are primarily mediated by ablation of afferent renal nerves; and 3) renal nerves do not contribute to the maintenance of renal inflammation in DOCA-salt hypertension.

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Section: Discussionsupporting

confidence: 56%

Targeted afferent renal denervation reduces arterial pressure but not renal inflammation in established DOCA-salt hypertension in the rat

Banek

Gauthier

Baumann

et al. 2018

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Predictably, these trials generated a large amount of interest and excitement for this alternative approach to treat resistant HTN. In recent years, several clinical studies [8][9][10][11][12][13][14][15] consistently report a significant and lasting antihypertensive response, most notably in the SPYRAL HTN-OFF MED, SPYRAL HTN-ON MED, and RADIANCE trials 16,17 .…”

Section: Introductionmentioning

confidence: 99%

Renal Inflammation in DOCA-Salt Hypertension

et al. 2019

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Recent reports indicate that, in addition to treating hypertension, renal denervation (RDN) also mitigates renal inflammation. However, since RDN decreases renal perfusion pressure, it is unclear whether these effects are due to the direct effects of RDN on inflammatory signaling or secondary to decreased arterial pressure (AP). Therefore, this study was conducted to elucidate the contribution of renal nerves to renal inflammation in the DOCA-salt rat, a model in which RDN decreases AP and abolishes renal inflammation. In Experiment 1, we assessed the temporal changes in renal inflammation by measuring renal cytokines and AP in DOCA-salt rats. Uninephrectomized (1K) adult male Sprague Dawley rats that received surgical renal denervation (RDN) or sham (Sham) were administered DOCA (100mg, s.c.) and 0.9% saline for 21 days. AP was measured by radiotelemetry, and urinary cytokine excretion were measured repeatedly. In Experiment 2, the contribution of renal nerves in renal inflammation was assessed in a 2-kidney DOCA-salt rat to control for renal perfusion pressure. DOCA-salt treatment was administered after unilateral (U-)RDN. In Experiment 1, DOCA-salt induced increases in AP and renal inflammation (assessed by urinary cytokines) were attenuated by RDN versus Sham. In Experiment 2, GRO/KC, MCP-1, and macrophage infiltration were lower in the denervated kidney vs. the contralateral Sham kidney. No differences in T-cell infiltration were observed. Together, these data support the hypothesis that renal nerves mediate, in part, the development of renal inflammation in the DOCA-salt rat independent of hypertension. The mechanisms and cellspecificity mediating these effects require further investigation.

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“…Патогенетические механизмы, лежащие в основе данного процесса, до конца не ясны; определенную роль может играть изменение вегетатив-ной функции, в частности, гиперсимпатикотония. Ни один класс антигипертензивных препаратов отчетливо не доказал свою эффективность в отношении коррекции вариабельности, тогда как положительный эффект инвазивного лечения подтвержден в ряде исследований, включая метаанализы [9]. Нами впервые показано постепенное снижение вариабельности САД в течение трех лет, причем тем более выраженное, чем выше были исходные значения.…”

Section: Discussionunclassified

Long-term outcomes of renal denervation and related sex characteristics: data from a three-year follow-up

et al. 2021

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Aim. To study the long-term outcomes of renal denervation (RDN) within 3-year follow-up with an assessment of blood pressure (BP) changes, the severity of target organ damage and the levels of pro- and anti-inflammatory cytokines in patients with resistant hypertension (RH), taking into account sex characteristics.Material and methods. A total of 42 patients with RH were examined at baseline, 1, 2, and 3 years after RDN on the background of antihypertensive therapy. Twenty-four-hour BP monitoring, echocardiography, assessment of creatinine level and estimated glomerular filtration rate (eGFR), as well as determination of some cytokines (interleukin (IL)-1β, 6, 10, tumor necrosis factor-α) were performed.Results. There was a persistent BP decrease in men and women for three years compared with the initial level by an average of 17 [4; 31]/10 [0; 18] mm Hg (p<0,05). Decrease in BP variability from 17,9±5,1 to 15,2±3,6 mm Hg was observed mainly by means of women, while the decrease in left ventricular mass from 250,4±64,0 to 229,3±61,9 g was mainly by means of men. Creatinine level was unchanged, while eGFR decreased from 78,8±16,1 to 74,5±20,3 ml/ min/1,73 m2 over 3 years; the mean eGFR decline was 1,4 ml/min/1,73 m2 in year. All studied cytokines tended to decrease regardless of sex: tumor necrosis factor-α — from 2,1 [1,2; 77] to 2,1 [1,7; 2,6] pg/ml (p=0,022); IL-1β — from 2,2 [1,5; 2,4] to 1,6 [1,1; 1,5] pg/ml (p=0,034); IL-6 — from 3,8 [1,6; 4,9] to 2,8 [1,8; 3,0] pg/ml (p>0,05), IL-10 — from 5,8 [3,2; 8,2] to 2,8 [2,6; 2,9] pg/ml (p=0,000), correlating with IL-6 dynamics.Conclusion. Three years after RDN, there is a persistent decrease in mean 24-hour BP, regardless of sex. In women, a more pronounced BP variability decrease is observed, while in men — regression of left ventricular mass. There is no significant decrease in eGFR in the long-term period. The decrease in proinflammatory cytokines maintains, and in some cases becomes more pronounced within three years after RDN.

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Blood pressure response to renal denervation is correlated with baseline blood pressure variability

Cited by 20 publications

References 42 publications

Targeted afferent renal denervation reduces arterial pressure but not renal inflammation in established DOCA-salt hypertension in the rat

Targeted afferent renal denervation reduces arterial pressure but not renal inflammation in established DOCA-salt hypertension in the rat

Renal Inflammation in DOCA-Salt Hypertension

Long-term outcomes of renal denervation and related sex characteristics: data from a three-year follow-up

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