Renal Denervation Therapy (RDT) in Resistant Hypertension

Resistant hypertension is defined as blood pressure that remains above therapeutic goal despite the use of three antihypertensive drugs including a diuretic. As much as one third of patients with arterial hypertension are treatmentrefractory as they do not reach sufficient blood pressure control despite combination antihypertensive therapy of significant duration. The hyperactivity of sympathetic nervous system (SNS) in the occurrence of treatment-resistant long standing hypertension has been established both in animal models and in clinical practice. In these patients, the kidneys play a central role as an activator of the sympathetic nervous system. The failure of purely pharmacological approaches to treat resistant hypertension has stimulated interest in invasive device-based treatments based on old concepts. In the absence of orally active antihypertensive agents, patients with severe and complicated hypertension were widely treated by surgical denervation of the kidneys until the 1960s, but this approach was associated with a high incidence of severe adverse events and a high mortality rate. A new catheter system using radiofrequency energy has been developed, allowing an endovascular approach to renal denervation and providing patients, with resistant hypertension, with a new therapeutic option that is minimally invasive and can be performed rapidly under local anaesthesia. With this method the afferent and efferent sympathetic nervous fibers surrounding the renal artery are ablated precisely keeping the renal artery intact. To date, this technique has been evaluated only in open-label trials including small numbers of highly selected resistant hypertensive patients with suitable renal artery anatomy. The available evidence suggests a significant and persistent blood pressure-lowering effect and a very low incidence of short & long term complications with no deleterious effects on renal function. These data, although promising, need confirmation in larger randomized controlled clinical trials with longerterm follow-up.DOI: http://dx.doi.org/10.3329/birdem.v2i2.12325(Birdem Med J 2012; 2(2): 104-112)

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SPECULATIONS ОN BLOOD PRESSURE INCREASE MECHANISMS IN RENAL ARTERY CLIPPED WISTAR RATS

Arterial’naya Gipertenziya (Arterial Hypertension) ◽

10.18705/1607-419x-2013-19-3-221-226 ◽

2013 ◽

Vol 19 (3) ◽

pp. 221-226

Author(s):

N. V. Kuzmenko ◽

M. G. Pliss ◽

N. S. Rubanova ◽

V. A. Tsyrlin

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Renal Artery ◽

Renovascular Hypertension ◽

Wistar Rats ◽

Renal Denervation ◽

Renal Nerves ◽

Blood Pressure Elevation ◽

Sympathetic Nervous

Objective.To examine the mechanisms underlying the activation of the sympathetic nervous system and blood pressure elevation in vasorenal hypertension in the male Wistar rats weighing 250–300 g.Design and methods.We observed the development of renovascular hypertension, beat-to-beat interval and heart rate variability in animals with intact renal nerves and denervated ischemic kidney for 8 weeks after renal artery clamping. Eight weeks later after renal artery clamping in hypertensive rats with denervated ischemic kidney, both-sided renal denervation was performed, and blood pressure was monitored for 6 weeks.Results.Although the ischemic kidney denervation reduces the activity of the sympathetic nervous system, it does not prevent renovascular hypertension development. However, both-sided renal denervation leads to the normalization of blood pressure in the rats with stable renovascular hypertension.Conclusion.We suggest that increased afferent fl ow from structural formations of the ischemic kidney plays an important role for the increased sympathetic nervous system activity.

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Abstract 291: Antihypertensive Effect Of Bia 5-1058 a New Selective Peripheral Dopamine β-hydroxylase Inhibitor

Hypertension ◽

10.1161/hyp.60.suppl_1.a291 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Bruno Igreja ◽

Nuno M Pires ◽

Lyndon C Wright ◽

Patrío Soares-da-Silva

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Receptor Antagonist ◽

Antihypertensive Effect ◽

Antihypertensive Drugs ◽

Radio Telemetry ◽

Sympathetic Nerves ◽

Maximum Reduction ◽

Sympathetic Nervous

The sympathetic nervous system can alter blood pressure by modulation of cardiac output, peripheral vascular resistance and renal function. One strategy for controlling sympathetic nerve function is to reduce the biosynthesis of norepinephrine (NE) via inhibition of dopamine β-hydroxylase (DβH; EC 1.14.17.1 ), the enzyme that catalyses the conversion of dopamine (DA) to NE in sympathetic nerves. BIA 5-1058 is a reversible DβH inhibitor that decreases NE levels in peripheral sympathetically innervated tissues slowing down sympathetic nervous system drive, without effect in brain tissues. In freely moving SHR implanted with radio-telemetry transmitters single administration of BIA 5-1058 showed a dose (3, 30 and 100 mg/Kg) and time dependent effect on blood pressure with no significant effect on heart rate (HR) and total activity monitored over a 96-hour period. The maximum reduction on systolic blood pressure (SBP) was -10.8, -21.1 and -35.2 mmHg for 3, 30 and 100 mg/Kg, respectively and the maximum reduction on diastolic blood pressure (DBP) was -9.9, -18.4 and -24.8 mmHg for 3, 30 and 100 mg/Kg, respectively. The antihypertensive effect of BIA 5-1058 (30 mg/Kg) was further evaluated in combination with efficacious doses of well-known antihypertensive drugs, like the ACE inhibitor captopril, the AT1 receptor antagonist losartan, the diuretic hydrochlorothiazide, beta-blocker metoprolol, the alpha-1 receptor antagonist prazosin, and the calcium channel blocker diltiazem. All drugs were administered orally (single dose) in a cross-over design and the effect was monitored for 72 hours. The combination of BIA 5-1058 with any of the tested antihypertensive drugs caused a stronger and prolonged blood pressure decrease than any of the compounds alone.In conclusion, peripheral DβH inhibitors can be used, alone or in combination with others antihypertensive drugs, to reduce blood pressure.

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Response to Blood Pressure and Sympathetic Nervous System Response to Renal Denervation

Hypertension ◽

10.1161/hypertensionaha.111.00520 ◽

2013 ◽

Vol 61 (2) ◽

Author(s):

Karsten Heusser ◽

Jens Tank ◽

Julia Brinkmann ◽

Bernhard Schmidt ◽

Jan Menne ◽

...

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Renal Denervation ◽

System Response ◽

Sympathetic Nervous

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Contribution of Selected Vasoactive Systems to Blood Pressure Regulation in Two Models of Chronic Kidney Disease

Physiological Research ◽

10.33549/physiolres.934392 ◽

2020 ◽

pp. 405-414

Author(s):

N DRÁBKOVÁ ◽

S HOJNÁ ◽

J ZICHA ◽

I VANĚČKOVÁ

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Chronic Kidney Disease ◽

Nervous System ◽

Kidney Disease ◽

Sympathetic Nervous System ◽

Renal Artery ◽

Partial Nephrectomy ◽

Wistar Rats ◽

Sympathetic Nervous

It is generally accepted that angiotensin II plays an important role in high blood pressure (BP) development in both 2-kidney-1-clip (2K1C) Goldblatt hypertension and in partial nephrectomy (NX) model of chronic kidney disease (CKD). The contribution of sympathetic nervous system and nitric oxide to BP control in these models is less clear. Partial nephrectomy or stenosis of the renal artery was performed in adult (10-week-old) male hypertensive heterozygous Ren-2 transgenic rats (TGR) and normotensive control Hannover Sprague Dawley (HanSD) rats and in Wistar rats. One and four weeks after the surgery, basal blood pressure (BP) and acute BP responses to the consecutive blockade of renin-angiotensin (RAS), sympathetic nervous (SNS), and nitric oxide (NO) systems were determined in conscious rats. Both surgical procedures increased plasma urea, a marker of renal damage; the effect being more pronounced following partial nephrectomy in hypertensive TGR than in normotensive HanSD rats with a substantially smaller effect in Wistar rats after renal artery stenosis. We demonstrated that the renin-angiotensin system does not play so fundamental role in blood pressure maintenance during hypertension development in either CKD model. By contrast, a more important role is exerted by the sympathetic nervous system, the activity of which is increased in hypertensive TGR-NX in the developmental phase of hypertension, while in HanSD-NX or Wistar-2K1C it is postponed to the established phase. The contribution of the vasoconstrictor systems (RAS and SNS) was increased following hypertension induction. The role of NO-dependent vasodilation was unchanged in 5/6 NX HanSD and in 2K1C Wistar rats, while it gradually decreased in 5/6 NX TGR rats.

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Blood pressure response to chronic episodic hypoxia: role of the sympathetic nervous system

Journal of Applied Physiology ◽

10.1152/jappl.1997.83.1.95 ◽

1997 ◽

Vol 83 (1) ◽

pp. 95-101 ◽

Cited By ~ 147

Author(s):

Gang Bao ◽

Naira Metreveli ◽

Rena Li ◽

Addison Taylor ◽

Eugene C. Fletcher

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Renal Artery ◽

Adrenal Medulla ◽

Blood Pressure Response ◽

Episodic Hypoxia ◽

Sympathetic Nervous ◽

Renal Artery Denervation

Bao, Gang, Naira Metreveli, Rena Li, Addison Taylor, and Eugene C. Fletcher. Blood pressure response to chronic episodic hypoxia: role of the sympathetic nervous system. J. Appl. Physiol. 83(1): 95–101, 1997.—Previous studies in several strains of rats have demonstrated that 35 consecutive days of recurrent episodic hypoxia (7 h/day) cause an 8- to 13-mmHg persistent increase in diurnal systemic blood pressure (BP). Carotid chemoreceptors and the sympathetic nervous system have been shown to be necessary for development of this BP increase. The present study was undertaken to further define the role of renal artery sympathetic nerves and the adrenal medulla in this BP increase. Male Sprague-Dawley rats had either adrenal medullectomy, bilateral renal artery denervation, or sham surgery. Rats from each of these groups were subjected to episodic hypoxia for 35 days. Control groups received either compressed air or were left unhandled. Adrenal demedullation or renal artery denervation eliminated the chronic diurnal mean BP response (measured intra-arterially) to episodic hypoxia, whereas sham-operated controls continued to showed persistent elevation of systemic BP. Plasma and renal tissue catecholamine levels at the end of the experiment confirmed successful adrenal demedullation or renal denervation in the respective animals. The chronic episodic hypoxia-mediated increase in diurnal BP requires both intact renal artery nerves as well as an intact adrenal medulla.

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Renal Denervation – a Modern Option for Treating Resistant Hypertension

Journal of Interdisciplinary Medicine ◽

10.2478/jim-2020-0002 ◽

2020 ◽

Vol 5 (1) ◽

pp. 19-22

Author(s):

Ioana Rodean ◽

Călin Chibelean

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Nervous System ◽

Cardiovascular Risk ◽

Resistant Hypertension ◽

Renal Denervation ◽

Efficacy And Safety ◽

Important Health ◽

Sympathetic Nervous ◽

New Treatment

AbstractHypertension is one of the main cardiovascular risk factors, and it remains an important health problem, demonstrating an increasing incidence despite new treatment methods. Numerous risk factors that can lead to the development of difficult-to-treat or resistant hypertension have been described in the literature in recent years. In this type of hypertension, an important role is played by the sympathetic nervous system. Especially in these cases, with a sympathetic overactivation, renal denervation has proven its efficacy and safety in lowering blood pressure. In this brief clinical update, we present the results of the main studies regarding the efficacy and safety of the renal denervation technique used in the treatment of resistant hypertension.

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