The sympathetic nervous system in hypertension due to unilateral renal artery stenosis in man

1. The validity of plasma noradrenaline as an index of sympathetic nervous activity was assessed by estimating variation in individual organ contribution to circulating concentrations. 2. Arteriovenous (A—V) differences in noradrenaline and adrenaline concentration were measured across several organs in nine patients with mild essential hypertension, in five with renal artery stenosis and 15 phaeochromocytoma patients. 3. In patients with phaeochromocytomas the percentage extraction of noradrenaline and adrenaline (estimated from the A—V differences) was similar across all organs, suggesting that adrenaline extraction could be used as a marker for noradrenaline extraction. 4. In the non-tumour patients the A—V difference for noradrenaline was less than that for adrenaline across most organs studied, reflecting the net result of noradrenaline release and extraction. The estimated contribution of various organs to the noradrenaline concentrations in their venous effluent was: heart. 21%; kidney 47%; legs 68%. 5. This pattern of A—V difference proved a positive diagnostic feature for non-tumour patients since it was not found even in the patients with small phaeochromocytomas, whose peripheral venous noradrenaline concentration alone did not distinguish them. 6. The venous-arterial difference across the adrenal glands of non-tumour patients was more than 10-fold greater for adrenaline than that for noradrenaline. Since the mean arterial concentration of noradrenaline was more than fivefold higher than that of adrenaline, the normal adrenal contribution to circulating noradrenaline is likely to be less than 2%. 7. In the patients with renal artery stenosis renal venous concentrations of noradrenaline (from the ischaemic kidney) were higher than arterial values, but mean arterial values were no higher than in the essential hypertensive patients. 8. Local variations in sympathetic activity may occur without altering the plasma noradrenaline concentration measured in peripheral plasma.

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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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Renal Denervation Therapy (RDT) in Resistant Hypertension

BIRDEM Medical Journal ◽

10.3329/birdem.v2i2.12325 ◽

2012 ◽

Vol 2 (2) ◽

pp. 104-112

Author(s):

Mohammad Gaffar Amin ◽

Hasna Fahmima Haque

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Renal Artery ◽

Resistant Hypertension ◽

Renal Denervation ◽

Antihypertensive Drugs ◽

Antihypertensive Agents ◽

Radiofrequency Energy ◽

Sympathetic Nervous

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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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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Barodenervation of the sympathetic nervous system of the renal artery. A new concept

International Journal of Cardiology ◽

10.1016/j.ijcard.2013.06.152 ◽

2013 ◽

Vol 168 (4) ◽

pp. 4443-4444 ◽

Cited By ~ 3

Author(s):

Christodoulos Stefanadis ◽

Andreas Synetos ◽

Konstantinos Toutouzas ◽

Costas Tsioufis ◽

Maria Drakopoulou ◽

...

Keyword(s):

Nervous System ◽

Sympathetic Nervous System ◽

Renal Artery ◽

Sympathetic Nervous

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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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Plasma Noradrenaline and Renovascular Hypertension in the Rat

Clinical Science ◽

10.1042/cs051439s ◽

1976 ◽

Vol 51 (s3) ◽

pp. 439s-442s

Author(s):

J. L. Reid ◽

H. J. Dargie ◽

S. S. Franklin ◽

Beverly Fraser

Keyword(s):

Nervous System ◽

Sympathetic Nervous System ◽

Renal Artery ◽

Renovascular Hypertension ◽

Plasma Noradrenaline ◽

Hypertensive Rats ◽

Contralateral Kidney ◽

Sympathetic Nervous ◽

Peripheral Sympathetic Nervous System

1. Plasma noradrenaline was measured in groups of rats up to 4 weeks after application of a renal artery clip. 2. When renal artery clipping was accompanied by contralateral nephrectomy (one-kidney model) plasma noradrenaline was significantly higher in hypertensive rats than in sham-operated control rats at 7, 14 and 28 days. 3. Plasma noradrenaline was not altered at any time examined in the two-kidney model (unilateral clip and contralateral kidney left in situ). 4. Neurogenic mechanisms mediated by the peripheral sympathetic nervous system appear to participate in the development of one-kidney renovascular hypertension, but do not play a significant role in the two-kidney model.

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