Sequential nephron blockade versus sequential renin–angiotensin system blockade in resistant hypertension

Bobrie, Guillaume; Frank, Michael; Azizi, Michel; Peyrard, Séverine; Boutouyrie, Pierre; Châtellier, Gilles; Laurent, Stéphane; Ménard, Joël; Plouin, Pierre‐François

doi:10.1097/hjh.0b013e3283551e98

Cited by 118 publications

(80 citation statements)

References 30 publications

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“…Given the high prevalence of drug therapy-resistant hypertension according to the currently used clinical criteria 32,33 and the increased cardiovascular risk in these patients, 34 new concepts to treat the condition more effectively are urgently needed. Intensive lifestyle interventions including aerobic exercise ameliorate hypertension in these patients.…”

Section: Perspectivesmentioning

confidence: 99%

“…35 Moreover, in a recent study, 58% of patients with uncontrolled hypertension on triple antihypertensive therapy achieved their blood pressure goal when sequential pharmacological nephron blockade was added. 33 Device-based antihypertensive treatments, such as catheter-based renal nerve ablation or electrical carotid sinus stimulation, are promising new approaches for patients not responding to intense pharmacological therapy. Moreover, these therapies provide unique insight in human cardiovascular physiology.…”

Section: Perspectivesmentioning

confidence: 99%

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Catheter-Based Renal Nerve Ablation and Centrally Generated Sympathetic Activity in Difficult-to-Control Hypertensive Patients

et al. 2012

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5Catheter-based renal nerve ablation decreased renal norepinephrine spillover, reflecting efferent activity by 47%. 2 The mechanisms likely contribute to the blood pressure-lowering effect because efferent renal sympathetic nerves activate the renin-angiotensin system 6,7 and directly stimulate tubular sodium retention. 8,9 In addition, reduced afferent renal nerve traffic may have elicited a central nervous sympatholytic response. Indeed, massive reductions in muscle sympathetic nerve activity (MSNA) and systemic norepinephrine spillover have been reported in a single patient after renal nerve ablation.10 Similarly, removal of the diseased native kidney reduced MSNA in renal transplant recipients.11 These clinical observations translate the experimental finding that renal afferents convey signals to the brain, thus raising sympathetic activity and blood pressure 12,13 from animals to humans. See Editorial Commentary, pp 1385-1386Abstract-Endovascular renal nerve ablation has been developed to treat resistant hypertension. In addition to lowering efferent renal sympathetic activation, the intervention may attenuate central sympathetic outflow through decreased renal afferent nerve traffic, as evidenced by a recent case report. We tested the hypothesis in 12 nonpreselected patients with difficult-to-control hypertension (aged 45-74 years) admitted for renal nerve ablation. All patients received ≥3 antihypertensive medications at full doses, including a diuretic. Electrocardiogram, respiration, brachial and finger arterial blood pressure, and muscle sympathetic nerve activity were recorded before and 3 to 6 months after renal nerve ablation. Heart rate and blood pressure variability were analyzed in the time and frequency domain. Pharmacological baroreflex slopes were determined using the modified Oxford bolus technique. Resting heart rate was 61±3 bpm before and 58±2 bpm after ablation (P=0.4). Supine blood pressure was 157±7/85±4 mm Hg before and 157±6/85±4 mm Hg after ablation (P=1.0). Renal nerve ablation did not change resting muscle sympathetic nerve activity (before, 34±2 bursts per minute; after, 32±3 bursts per minute P=0.6), heart rate variability, or blood pressure variability. Pharmacological baroreflex control of heart rate and muscle sympathetic nerve activity did not change. We conclude that reduced central sympathetic inhibition may be the exception rather than the rule after renal nerve ablation in unselected patients with difficult-to-control arterial hypertension. (Hypertension. 2012;60:1485-1490.) • Online Data Supplement

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Section: Perspectivesmentioning

confidence: 99%

Section: Perspectivesmentioning

confidence: 99%

Catheter-Based Renal Nerve Ablation and Centrally Generated Sympathetic Activity in Difficult-to-Control Hypertensive Patients

et al. 2012

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“…8 Before handing management of resistant hypertension over to the interventionists, however, there is evidence that pharmacological management could be improved with evidence-based regimens. [9][10][11][12] There is a need for rigorous trial design, comparisons with benchmark pharmacotherapy, and better classification of patient groups that will benefit from renal denervation therapy. Extension of indications beyond that supported by trial data should be monitored and generally avoided.…”

Section: Hypertensionmentioning

confidence: 99%

Recent Clinical Trials of Hypertension Management

Jennings

2013

Hypertension

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“…Serious adverse events did not differ significantly between groups. 67 Thus, sequential diuretic use appeared to be more effective than sequential RAAS blockade for BP lowering without any excess in adverse events.…”

Section: Pharmacotherapy: Nondiureticsmentioning

confidence: 99%

Apparent Treatment-Resistant Hypertension and Chronic Kidney Disease: Another Cardiovascular-Renal Syndrome?

Vemulapalli

Tyson

Svetkey

2014

Advances in Chronic Kidney Disease

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To identify patients at increased risk of cardiovascular (CV) outcomes, apparent treatment-resistant hypertension (aTRH) is defined as having a blood pressure above goal despite the use of 3 or more antihypertensive therapies of different classes at maximally tolerated doses, ideally including a diuretic. Recent epidemiologic studies in selected populations estimated the prevalence of aTRH as 10% to 15% among patients with hypertension and that aTRH is associated with elevated risk of CV and renal outcomes. Additionally, aTRH and CKD are associated. Although the pathogenesis of aTRH is multifactorial, the kidney is believed to play a significant role. Increased volume expansion, aldosterone concentration, mineralocorticoid receptor activity, arterial stiffness, and sympathetic nervous system activity are central to the pathogenesis of aTRH and are targets of therapies. Although diuretics form the basis of therapy in aTRH, pathophysiologic and clinical data suggest an important role for aldosterone antagonism. Interventional techniques, such as renal denervation and carotid baroreceptor activation, modulate the sympathetic nervous system and are currently in phase III trials for the treatment of aTRH. These technologies are as yet unproven and have not been investigated in relationship to CV outcomes or in patients with CKD.

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Sequential nephron blockade versus sequential renin–angiotensin system blockade in resistant hypertension

Abstract: In patients with resistant hypertension, sequential nephron blockade induces a large and well tolerated reduction in blood pressure via a progressive increase in sodium depletion, and is more effective than sequential renin-angiotensin system blockade.

Cited by 118 publications

References 30 publications

Catheter-Based Renal Nerve Ablation and Centrally Generated Sympathetic Activity in Difficult-to-Control Hypertensive Patients

Catheter-Based Renal Nerve Ablation and Centrally Generated Sympathetic Activity in Difficult-to-Control Hypertensive Patients

Recent Clinical Trials of Hypertension Management

Apparent Treatment-Resistant Hypertension and Chronic Kidney Disease: Another Cardiovascular-Renal Syndrome?

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