Blood pressure and neurohormonal responses to renal nerve ablation in treatment-resistant hypertension

Ezzahti, Mustafa; Moelker, Adriaan; Friesema, Edith C. H.; Linde, Nicole A.J. van der; Krestin, Gabriël P.; Meiracker, Anton H. van den

doi:10.1097/hjh.0b013e3283658ef7

Cited by 33 publications

(27 citation statements)

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“…13 Despite these proposed mechanisms, it is unknown how Abstract-Previous studies indicate that catheter-based renal denervation reduces blood pressure and renal norepinephrine spillover in human resistant hypertension. The effects of this procedure on afferent sensory and efferent sympathetic renal nerves, and the subsequent degree of reinnervation, have not been investigated.…”

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confidence: 99%

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Reinnervation of Renal Afferent and Efferent Nerves at 5.5 and 11 Months After Catheter-Based Radiofrequency Renal Denervation In Sheep

et al. 2015

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T here is extensive evidence that renal afferent and efferent nerves play a critical role in the control of renal function and in setting the level of arterial blood pressure.1 This includes the findings that in experimental and human hypertension there are increases in renal sympathetic nerve activity (RSNA) and renal norepinephrine spillover, respectively. In addition, surgical renal denervation (RDN) reduces blood pressure in hypertensive animals and patients, 1-4 although in patients this was associated with several side effects. 4 The development of catheter-based radiofrequency RDN has resulted in a resurgence of interest in RDN as a treatment for resistant hypertensive patients. Initial trials demonstrated reductions in office systolic blood pressure 5,6 and in the 36-month follow-up from the first trial 93% of patients showed reductions in office systolic blood pressure of ≥10 mm Hg after RDN. 7 In contrast, the recent Symplicity HTN-3 trial did not demonstrate reductions in systolic blood pressure beyond that observed in sham control patients 6 months after RDN, 8 although there is still debate on factors that may have led to the lack of effect, such as procedural and population variability.It would be expected that destruction of the renal nerves reduces blood pressure because the efferent renal nerves play a major role in stimulating renin release, causing renal vasoconstriction and inducing sodium retention.1 It is also plausible that in hypertension, increased afferent renal nerve activity may cause a reflex increase in sympathetic outflow and worsening hypertension.9,10 Such actions are supported by findings that in some hypertensive patients, catheter-based RDN reduced the level of muscle SNA 11,12 and plasma norepinephrine. 13 Despite these proposed mechanisms, it is unknown how Abstract-Previous studies indicate that catheter-based renal denervation reduces blood pressure and renal norepinephrine spillover in human resistant hypertension. The effects of this procedure on afferent sensory and efferent sympathetic renal nerves, and the subsequent degree of reinnervation, have not been investigated. We therefore examined the level of functional and anatomic reinnervation at 5.5 and 11 months after renal denervation using the Symplicity Flex catheter. In normotensive anesthetized sheep (n=6), electric stimulation of intact renal nerves increased arterial pressure from 99±3 to 107±3 mm Hg (afferent response) and reduced renal blood flow from 198±16 to 85±20 mL/min (efferent response). In a further group (n=6), immediately after denervation, renal sympathetic nerve activity was absent and the responses to electric stimulation were abolished. At 11 months after denervation (n=5), renal sympathetic nerve activity and the responses to electric stimulation were at normal levels. Immunohistochemical staining for renal efferent (tyrosine hydroxylase) and renal afferent nerves (calcitonin gene-related peptide), as well as renal norepinephrine levels, was normal 11 months after denervation. Findings at 5.5...

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confidence: 99%

“…9,10 Such actions are supported by findings that in some hypertensive patients, catheter-based RDN reduced the level of muscle SNA 11,12 and plasma norepinephrine. 13 Despite these proposed mechanisms, it is unknown how…”

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confidence: 99%

Reinnervation of Renal Afferent and Efferent Nerves at 5.5 and 11 Months After Catheter-Based Radiofrequency Renal Denervation In Sheep

et al. 2015

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“…2,5,18 This is also the case for the renin-angiotensin activation reported in resistant HT patients. 4,5, 18 Finally, this is the case for the elevated circulating plasma levels of endothelin-1 and the oxydative stress dysfunction described in patients with resistant HT. 5 These neurohumoral changes may be responsible for the after a 5-min occlusion, triggered a marked increase in blood flow.…”

Section: Resultsmentioning

confidence: 97%

“…At baseline, deflation of the cuff positioned at the brachial artery level, Second, it showed, again for the first time, that HEx training triggers in resistant HT patients a significant reduction in the circulating plasma levels of renin (and thus of angiotensin II with its pronounced vasocostrictive properties), which are again remarkably increased in this hypertensive state. 3-5, 18 Third, it provided evidence that the BP reduction elicited by HEx training is associated with an increase in the circulating plasma levels of NO and a parallel reduction in plasma concentrations of endothelin-1, a peptide produced by the endothelium with potent vasoconstrictor effects. 5, 6 Taken together these findings allow us to conclude that several of the neurohumoral alterations characterizing resistant HT and responsible, at least in part, for the marked systemic vasoconstriction and BP elevation detected in this condition are favorably affected by HEx.…”

Section: Resultsmentioning

confidence: 98%

Neurohumoral and Endothelial Responses to Heated Water-Based Exercise in Resistant Hypertensive Patients

Cruz¹,

Bocchi²,

Guimarães³

2017

Circ J

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155 patients with a diagnosis of resistant HT were screneed for the HEx trial in the HT outpatient clinic of the University Hospital of São Paulo, Brasil. We excluded 111 patients, with the remaining 44 patients included in the present study. They were sedentary, aged between 40 and 65 years, diagnosed as affected by resistant HT for more than 5 years, and who in the previous 6 months had unchanged and regular use of at least 3 optimally dosed antihypertensive drugs, including a diuretic, and displayed office systolic BP >140 mmHg, and/or diastolic BP >90 mmHg. 7 We used medical records to exclude patients with a history of secondary HT [e.g., chronic kidney disease (creatinine W e recently showed that heated water-based exercise (HEx) training exerts blood pressure (BP) lowering effects in patients with true resistant hypertension (HT) by significantly reducing office as well as ambulatory BP values recorded during a 24-h period. 1 Whether and to what extent these BP-lowering effects are associated with, and presumably triggered by, modifications in the behavior of the neurohumoral systems that participate in the homeostatic control of BP and are activated in resistant HT, such as the sympathetic nervous system and the renin-angiotensin-aldosterone axis, 2-5 is largely unknown. In addition, no information is available on whether and to what extent HEx training is capable of exerting favorable effects on the endothelial dysfunction that characterizes resistant HT patients. 5, 6 The present study was designed to provide information on the neurohumoral mechanisms of the BP-lowering effects of HEx training in resistant HT patients by assessing the sympathetic and renin-angiotensin as well as the Guido Grassi, MD; Guilherme Veiga Guimaraes, PhDBackground: The neurohumoral and endothelial responses to the blood pressure (BP) lowering effects of heated water-based

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“…Commentary plasma catecholamines, 9 improvements in insulin sensitivity, 10 reductions in plasma renin, 11 (although this has not been a consistent finding 9 ) and regression of left ventricular hypertrophy. 12 In general the technique has, however, been uncritically accepted and practised worldwide.…”

Section: Research-article2014mentioning

confidence: 98%

Resistant hypertension and renal denervation: Who’s kidding whom?

Sever¹

2014

J Renin Angiotensin Aldosterone Syst

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The renin-angiotensin-aldosterone system (RAAS) plays an important role in the homeostasis of blood pressure regulation. Its role in the pathophysiology of hypertension is, however, complex. Over-activation of the RAAS in severe and accelerated phase hypertension is generally recognised but its role in drug-resistant hypertension less clear. This is one question being addressed by the British Hypertension Society PATHWAY Trial Programme (www. bhsoc.org).The interrelationships between the RAAS and the sympathetic nervous system are also complex and extend from the central nervous system to the periphery, including post-ganglionic nerve endings, the adrenal gland and the kidney. It was therefore of considerable interest to note the impressive blood pressure reduction observed in early studies of renal denervation (RDN) in patients with apparent drug-resistant hypertension and observe to what extent neurohumoral changes accompanied the falls in blood pressure.By way of background, resistant hypertension is defined as blood pressure remaining above goal in spite of the concurrent use of three antihypertensive agents of different classes. Ideally one of these agents should be a diuretic, and all agents should be prescribed at optimal doses. Its true prevalence is unknown, but observational studies and clinical trials suggest that it is a common clinical problem. In an analysis of National Health and Nutrition Examination Survey (NHANES), 1 of participants being treated for hypertension only 53% were controlled to a blood pressure <140/90 mmHg. In those with diabetes or chronic kidney disease the percentage controlled was considerably less. Similar figures (63%) for all treated patients have recently been reported by the Health Survey for England 2 but, of course, many of the participants in these surveys were not receiving optimal treatment for their hypertension.Resistant hypertension comprises a heterogeneous group of patients including those with undiagnosed secondary hypertension, inaccurate blood pressure measurement, white coat hypertension and poor adherence with prescribed medication. In the author's experience true resistant hypertension is uncommon. Thus, in the evaluation of patients with apparent resistant hypertension, a comprehensive management algorithm should be applied which includes investigations to rule out secondary causes, confirmation of appropriate treatment (drugs and doses), including a trial of spironolactone, and formal assessment of drug compliance. This should include observed drug ingestion in the clinic followed by blood pressure monitoring for up to 4 hours and 24 hour ambulatory blood pressure monitoring thereafter. The post-dosing period of observation for 4 hours in the clinic is a precaution for cases where substantial falls in blood pressure occur in the hitherto non-compliant or poorly compliant patient. If the facility is available, urinary drug assays provide additional information on non-compliance.Only after the diligent exclusion of the majority of patients referred with so...

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Blood pressure and neurohormonal responses to renal nerve ablation in treatment-resistant hypertension

Cited by 33 publications

References 34 publications

Reinnervation of Renal Afferent and Efferent Nerves at 5.5 and 11 Months After Catheter-Based Radiofrequency Renal Denervation In Sheep

Reinnervation of Renal Afferent and Efferent Nerves at 5.5 and 11 Months After Catheter-Based Radiofrequency Renal Denervation In Sheep

Neurohumoral and Endothelial Responses to Heated Water-Based Exercise in Resistant Hypertensive Patients

Resistant hypertension and renal denervation: Who’s kidding whom?

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