The renal afferent nerves in the pathogenesis of hypertension

1987 ◽  
Vol 65 (8) ◽  
pp. 1548-1558 ◽  
Author(s):  
Suzanne Oparil ◽  
Wanida Sripairojthikoon ◽  
J. Michael Wyss
Keyword(s):  
Renal Denervation ◽  
Genetic Model ◽  
Spontaneously Hypertensive Rat ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Experimental Models ◽  
Renal Nerves ◽  
Renal Nerve ◽  
Afferent Nerves ◽  
Hypertensive Rat

The renal nerves play a role in the pathogenesis of hypertension in a number of experimental models. In the deoxycorticosterone acetate – salt (DOCA–NaCl) hypertensive rat and the spontaneously hypertensive rat (SHR) of the Okamoto strain, total peripheral renal denervation delays the development and blunts the severity of hypertension and causes an increase in urinary sodium excretion, suggesting a renal efferent mechanism. Further, selective lesioning of the renal afferent nerves by dorsal rhizotomy reduces hypothalamic norepinephrine stores without altering the development of hypertension in the SHR, indicating that the renal afferent nerves do not play a major role in the development of hypertension in this genetic model. In contrast, the renal afferent nerves appear to be important in one-kidney, one-clip and two-kidney, one-clip Goldblatt hypertensive rats (1K, 1C and 2K, 1C, respectively) and in dogs with chronic coarctation hypertension. Total peripheral renal denervation attenuates the severity of hypertension in these models, mainly by interrupting renal afferent nerve activity, which by a direct feedback mechanism attenuates systemic sympathetic tone, thereby lowering blood pressure. Peripheral renal denervation has a peripheral sympatholytic effect and alters the level of activation of central noradrenergic pathways but does not alter sodium or water intake or excretion, plasma renin activity or creatinine clearance, suggesting that efferent renal nerve function does not play an important role in the maintenance of this form of hypertension. Selective lesioning of the renal afferent nerves attenuates the development of hypertension, thus giving direct evidence that the renal afferent nerves participate in the pathogenesis of renovascular hypertension.

Neuronal control of the kidney: Contribution to hypertension

1992 ◽  
Vol 70 (5) ◽  
pp. 759-770 ◽  
Author(s):  
J. Michael Wyss ◽  
Suzanne Oparil ◽  
Wanida Sripairojthikoon
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Renal Denervation ◽  
Spontaneously Hypertensive Rat ◽  
Renal Nerves ◽  
Sodium Retention ◽  
Spontaneously Hypertensive ◽  
Afferent Nerves ◽  
Hypertensive Rat ◽  
Sympathetic Nervous

The renal nerves contribute to hypertension in experimental models of the disease, and appear to play a role in human hypertension. Several lines of evidence indicate that both in spontaneously hypertensive rats and in deoxycorticosterone acetate–NaCl rats, the full development of hypertension is dependent on renal efferent nerves and their induction of excess sodium retention. Renal sensory (afferent nerve) feedback to the central nervous system does not contribute to either of these forms of hypertension. In contrast, renovascular hypertension in rats and aortic coarctation hypertension in dogs are mediated, at least in part, by overactivity of renal afferent nerves and a resultant increase in systemic sympathetic nervous system activity. These forms of hypertension are not associated with sodium retention, and selective sensory denervation of renal afferent nerves by dorsal rhizotomy and total renal denervation result in similar reductions in hypertension. Surprisingly, the renal nerves do not contribute to dietary NaCl exacerbated hypertension in the spontaneously hypertensive rat, dietary NaCl-induced hypertension in the Dahl NaCl-sensitive rat, or the chronic hypertensive and nephrotoxic effects of cyclosporine A therapy in the rat, despite the finding that in all three forms of hypertension, overactivity of the sympathetic nervous system is prominent. Clinical studies indicate that the renal afferent and efferent nerves contribute to hypertension of different etiologies. Together these data point to the complex role that the renal nerves likely play in human essential hypertension.Key words: kidney, cyclosporine, spontaneously hypertensive rat, renal deafferentation, renal denervation.

Central effects of atrial natriuretic factor on renal salt excretion

1991 ◽  
Vol 261 (2) ◽  
pp. F354-F359 ◽  
Author(s):  
P. Rohmeiss ◽  
G. Demmert ◽  
T. Unger
Keyword(s):  
Sodium Excretion ◽  
Atrial Natriuretic Factor ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Renal Nerves ◽  
Urinary Flow ◽  
Renal Nerve ◽  
Ureteral Catheter ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

Atrial natriuretic factor (ANF) has been localized in periventricular brain areas involved in cardiovascular and fluid control. We investigated the effect of intracerebroventricular (icv) ANF (alpha-rat atriopeptin III) on renal sodium excretion in unilaterally nephrectomized, conscious unrestrained rats fitted with a chronic ureteral catheter. Isotonic NaCl (1 ml/h) was infused intravenously. ANF injected at doses (icv) of 1 ng (n = 6), 100 ng (n = 7), and 1 microgram (n = 7) reduced urinary sodium excretion (all values mumol/45 min, means +/- SE) from 111.6 +/- 24.4 to 83 +/- 20 (P less than 0.05), from 96.9 +/- 25.2 to 55 +/- 14 (P less than 0.01), and from 90.8 +/- 14.2 to 51 +/- 9 (P less than 0.01), respectively, whereas urinary flow rate did not change. The antinatriuretic effect was immediate in onset and lasted for greater than or equal to 60 min. Blood pressure remained unaltered. ANF (100 ng icv) increased efferent sympathetic renal nerve activity (+36%; n = 6, P less than 0.05), plasma renin activity (4.6 +/- 0.6 to 7.5 +/- 0.5 pmol angiotensin I.ml-1.h-1; n = 9, P less than 0.01), plasma angiotensin II (68.7 +/- 2.5 to 84.7 +/- 3.4 fmol/ml; n = 8, P less than 0.01), and aldosterone (22.3 +/- 3.6 to 37.2 +/- 4.0 ng/ml; n = 9, P less than 0.02). Renal denervation reduced the antinatriuretic effect of ANF by 37%. We conclude that brain ANF has antinatriuretic actions, which may be partly explained by activation of renal nerves.

Do renal nerves chronically influence renal function and arterial pressure in spinal rats?

1992 ◽  
Vol 263 (6) ◽  
pp. R1265-R1270 ◽  
Author(s):  
K. A. Trostel ◽  
J. W. Osborn
Keyword(s):  
Renal Function ◽  
Arterial Pressure ◽  
Cervical Spinal Cord ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Renal Nerves ◽  
Sprague Dawley ◽  
Urine Ph ◽  
Renal Nerve ◽  
Renal Nerve Activity

Previous studies have demonstrated that renal nerve activity has acute effects on renal function in rats with cervical spinal cord transection (CST). The present study tested the hypothesis that renal nerves chronically influence renal and cardiovascular function in CST rats. Three groups of conscious Sprague-Dawley rats were studied: renal denervated plus CST (RDNX + CST), sham RDNX plus CST (sham + CST), and sham RDNX plus sham CST (intact). CST or sham CST surgeries were performed 8 days after RDNX or sham RDNX. Sodium and water intakes were fixed by intravenous infusion. Mean arterial pressure (MAP) and plasma renin activity (PRA) were measured before and for 9 days after CST/sham CST. In addition, urine flow, urinary sodium excretion, and urine pH were measured in the two groups of CST rats. One day after CST, MAP decreased approximately 25 mmHg in both RDNX + CST and sham + CST groups. PRA had fallen approximately 50% 1 day after CST and was not different between CST groups. PRA remained depressed throughout the study. There were no differences between sham + CST and RDNX + CST rats in any of the renal or cardiovascular variables measured after CST. In summary, we found no evidence for a chronic effect of renal nerves on renal function or arterial pressure in CST rats.

Renal nerves and experimental hypertension: evidence and controversy

1987 ◽  
Vol 65 (8) ◽  
pp. 1540-1547 ◽  
Author(s):  
Robert L. Kline
Keyword(s):  
Renal Function ◽  
Arterial Pressure ◽  
Renal Denervation ◽  
Spontaneously Hypertensive Rat ◽  
Sodium Intake ◽  
Renal Nerves ◽  
Experimental Hypertension ◽  
Renal Nerve ◽  
Spontaneously Hypertensive ◽  
Hemodynamic Variables

Noradrenergic fibers innervate various parts of the nephron and can contribute to sodium and water homeostasis by influencing hemodynamic variables, tubular reabsorptive mechanisms, and renin release. As renal function is considered to be a primary determinant of arterial pressure, efferent renal nerves may be an important link between the central nervous system and the kidney in the development and maintenance of hypertension. Little is known about the relative importance of renal nerves and their interactions with other factors in influencing renal function chronically. There is disagreement about the evidence for enhanced noradrenergic drive to the kidney in hypertensive rats, as the renal nerve firing rate, neurotransmitter release and metabolism, and receptor properties are generally not studied in association with measurements of renal function. However, chronic renal denervation has been shown to significantly affect arterial pressure in diverse forms of experimental hypertension in rats, including genetic models, as well as renovascular, mineralocorticoid, neurogenic, and angiotensin II hypertension. The actual mechanisms responsible for this effect of renal denervation are not clear, but presumably reflect changes in the arterial pressure – urinary sodium output relationship. On the whole, there is reasonable correlation between neurophysiological, biochemical, and renal denervation studies in the spontaneously hypertensive rat, suggesting that renal nerves do play a role in the onset of hypertension in these animals. The effect of renal denervation in other models of hypertension seems less clear, with recent reports showing that renal denervation does not alter the hypertensive process in renovascular, mineralocorticoid, and salt-related hypertension. These contradictory findings are not easily explained, but there is some indication that elevated sodium intake may alter the response to renal denervation. Resolution of these controversies must await a better understanding of the influence of renal nerves on renal function and arterial pressure in normal and hypertensive animals.

Abstract 289: Effect of Central Sympatholytic Treatment on the Anti-Hypertensive Response of Renal Denervation in the Spontaneously Hypertensive Rat

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Jeremiah Phelps ◽  
Gregory Fink
Keyword(s):  
Renal Denervation ◽  
Multivariate Analyses ◽  
Spontaneously Hypertensive Rat ◽  
Clinical Success ◽  
Renal Nerve ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Precise Understanding ◽  
Renal Nerve Ablation ◽  
Effective Doses

Renal nerve ablation has been shown to elicit a chronic, anti-hypertensive effect in drug-resistant hypertensive patients. Precise understanding of the mechanisms underlying the clinical success of renal denervation is currently unknown, and as a consequence, it is predicted the technology will be under-utilized until such information is uncovered. Retrospective multivariate analyses of responders suggest treatment with a central sympatholytic may correlate with a successful response to renal denervation. However, this hypothesis remains untested. This study tested the hypothesis that pretreatment with a central sympatholytic would augment the response to renal denervation (RDX) in the spontaneously hypertensive rat. In rats pre-treated for 1 week with clonidine (125ug/kg/day), MAP was significantly reduced from baseline but there was no difference in response to clonidine between groups (Sham(n=7): -21.3±0.8 vs RDX(n=7): -22.8±1.3mmHg, p>0.05). During clonidine treatment RDX significantly reduced MAP within 48hrs in RDX animals compared to shams (Sham: 145.9±2.5 vs. RDX: 135.0±1.7mmHg, p<0.05). However, this reduction was abolished by day 5 after RDX (Sham: 145.1±2.5 vs RDX: 140.4±3.0 mmHg, p>0.05). Discontinuation of clonidine caused blood pressure to rise, but once pressures stabilized, the average MAP was significantly lower in RDX treated rats (Sham:157.4 ± 0.8 vs. RDX: 146.4 ± 0.8mmHg, p<0.05). Administration of hydralazine, which reflexively increases sympathetic activity, lowered MAP similar to the magnitude observed in clonidine treatment (Sham: -19.6±1.0 vs RDX: -18.2±0.9mmHg). The anti-hypertensive effect of RDX was not augmented by hydralaizine however, it was also not abolished. These findings do not support the idea that patients taking effective doses of centrally acting sympatholytics will enhance the response to renal denervation.

Renal denervation alters cardiovascular and endocrine responses to hemorrhage in conscious newborn lambs

1998 ◽  
Vol 275 (1) ◽  
pp. H285-H291 ◽  
Author(s):  
Francine G. Smith ◽  
Isam Abu-Amarah
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Renal Denervation ◽  
Plasma Renin ◽  
Sympathetic Nerves ◽  
Renal Nerves ◽  
Elevated Plasma ◽  
Baseline Levels ◽  
Renal Sympathetic

To investigate the role of renal sympathetic nerves in modulating cardiovascular and endocrine responses to hemorrhage early in life, we carried out three experiments in conscious, chronically instrumented lambs with intact renal nerves (intact; n = 8) and with bilateral renal denervation (denervated; n = 5). Measurements were made 1 h before and 1 h after 0, 10, and 20% hemorrhage. Blood pressure decreased transiently after 20% hemorrhage in intact lambs and returned to control levels. In denervated lambs, however, blood pressure remained decreased after 60 min. After 20% hemorrhage, heart rate increased from 170 ± 16 to 207 ± 18 beats/min in intact lambs but not in denervated lambs, in which basal heart rates were already elevated to 202 ± 21 beats/min. Despite an elevated plasma renin activity (PRA) measured in denervated (12.0 ± 6.4 ng ANG I ⋅ ml−1 ⋅ h−1) compared with intact lambs (4.0 ± 1.1 ng ANG I ⋅ ml−1 ⋅ h−1), the increase in PRA in response to 20% hemorrhage was similar in both groups. Plasma levels of arginine vasopressin increased from 11 ± 8 to 197 ± 246 pg/ml after 20% hemorrhage in intact lambs but remained unaltered in denervated lambs from baseline levels of 15 ± 10 pg/ml. These observations provide evidence that in the newborn, renal sympathetic nerves modulate cardiovascular and endocrine responses to hemorrhage.

scholarly journals Early Morphologic Alterations in Renal Artery Wall and Renal Nerves in Response to Catheter-Based Renal Denervation Procedure in Sheep: Difference Between Single-Point and Multiple-Point Ablation Catheters

2017 ◽  
pp. 601-614 ◽  
Author(s):  
M. TÁBORSKÝ ◽  
D. RICHTER ◽  
Z. TONAR ◽  
T. KUBÍKOVÁ ◽  
A. HERMAN ◽  
...  
Keyword(s):  
Renal Artery ◽  
Resistant Hypertension ◽  
Renal Denervation ◽  
Single Point ◽  
Renal Tissue ◽  
Renal Nerves ◽  
Multiple Point ◽  
Renal Nerve ◽  
Jude Medical ◽  
Novel Strategy

Renal sympathetic hyperactivity is critically involved in hypertension pathophysiology; renal denervation (RDN) presents a novel strategy for treatment of resistant hypertension cases. This study assessed effects of two RDN systems to detect acute intravascular, vascular and peri-vascular changes in the renal artery, and renal nerve alterations, in the sheep. The procedures using a single-point or multi-point ablation catheters, Symplicity FlexTM, Medtronic versus EnligHTNTM, St. Jude Medical were compared; the intact contralateral kidneys served as controls. Histopathological and immunohistochemical assessments were performed 48 h after RDN procedures; the kidney and suprarenal gland morphology was also evaluated. Special staining methods were applied for histologic analysis, to adequately score the injury of renal artery and adjacent renal nerves. These were more pronounced in the animals treated with the multi-point compared with the single-point catheter. However, neither RDN procedure led to complete renal nerve ablation. Forty-eight hours after the procedure no significant changes in plasma and renal tissue catecholamines were detected. The morphologic changes elicited by application of both RDN systems appeared to be dependent on individual anatomical variability of renal nerves in the sheep. Similar variability in humans may limit the therapeutic effectiveness of RDN procedures used in patients with resistant hypertension.

Abstract P203: Insights To Lesion Formation For Percutaneous Renal Denervation: Human And Porcine Histological Analyses

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
David Kandzari ◽  
Stefan Tunev ◽  
Markus P Schlaich ◽  
David P LEE ◽  
Aloke Finn ◽  
...  
Keyword(s):  
Renal Denervation ◽  
Renal Arteries ◽  
Renal Nerves ◽  
Swine Model ◽  
Renal Nerve ◽  
Perivascular Adipose Tissue ◽  
Human Cadavers ◽  
Procedural Outcomes ◽  
Maximal Reduction ◽  
Conduction Properties

Background: The safety and efficacy of radiofrequency (RF) renal denervation (RDN) have been demonstrated in multiple randomized trials. We performed histological analyses in a swine model and human cadavers to investigate RF lesion geometry, morphology and location in the context of local anatomic structures and describe their impact on procedural outcomes. Methods: The Symplicity Spyral catheter was used to perform RDN in 164 renal arteries from healthy swine terminated at 7 days post-treatment. Lesion characteristics were determined by semi-quantitative histology. Renal nerve functionality was measured by quantitative immunohistochemistry and correlated to renal norepinephrine. In addition, we investigated the retroperitoneal space in 10 human cadavers to determine the relative location of extravascular tissues. Results: In the swine model, RF lesions developed exclusively in the perivascular adipose tissue which contains the renal nerves. Lesions were irregularly shaped due to inherent sparing of surrounding perfused structures, such as veins and lymph nodes. Maximum depth of the irregularly shaped RF lesions was 6.8±2.5 mm, and mean depth was 3.9±2.4 mm. Renal norepinephrine levels were lowest when >80% of renal nerves were ablated ( Figure ). Reendothelialization of the lesion area was >99% within 7 days. In humans, only 0.3% of renal nerves were localized on the opposite side of the renal veins. Conclusion: Patterns of RF RDN are uniquely influenced by electrical and thermal conduction properties of tissues surrounding the renal arteries. Maximal reduction of renal norepinephrine content requires ablation of at least 80% of the renal nerves.

The kidneys stimulate vasopressin release during hemorrhage in rats with chronic NTS lesions

1997 ◽  
Vol 272 (5) ◽  
pp. R1540-R1551 ◽  
Author(s):  
A. M. Schreihofer ◽  
G. E. Hoffman ◽  
A. F. Sved
Keyword(s):  
Renal Denervation ◽  
Critical Role ◽  
Plasma Renin ◽  
Afferent Input ◽  
Renal Nerves ◽  
Solitary Tract ◽  
Vasopressin Release ◽  
Afferent Signal ◽  
The Brain ◽  
Intact Rats

Elimination of baroreceptor afferent input to the brain produced by chronic lesion of nucleus of the solitary tract (NTS) does not alter vasopressin (VP) release during hypotensive hemorrhage in conscious rats. To investigate whether the kidneys play a critical role in stimulating VP release during hemorrhage in chronic NTS-lesioned rats, we examined the effects of removing potential signals arising from the kidneys. In NTS-lesioned rats, nephrectomy or renal denervation, but not captopril injection, markedly attenuated (but did not abolish) hemorrhage-induced VP release. In contrast, none of these manipulations attenuated the VP response in NTS-intact rats. Hemorrhage increased plasma renin activity in control and NTS-lesioned rats, and this response was not altered by renal denervation. In rats with NTS lesions and renal denervation, hemorrhage induced the expression of Fos in hypothalamic magnocellular VP neurons in a pattern similar to that of hemorrhage in intact rats. Collectively, these results indicate that in chronic NTS-lesioned rats an afferent signal arising from the kidneys stimulates VP release during hemorrhage, possibly through renal nerves. However, with the NTS intact or after the selective removal of arterial baroreceptor inputs, such a role for the kidneys is not apparent. Furthermore, in the absence of the NTS and renal nerves, another signal generated by hypotensive hemorrhage continues to stimulate VP neurons.

Effect of renal denervation on the suppression of renin secretion by vasopressin in conscious dogs

1984 ◽  
Vol 247 (6) ◽  
pp. F881-F887 ◽  
Author(s):  
L. C. Gregory ◽  
I. A. Reid
Keyword(s):  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Renal Denervation ◽  
Plasma Renin ◽  
Renin Secretion ◽  
Conscious Dogs ◽  
Reflex Response ◽  
Renal Nerves ◽  
Ang Ii ◽  
Before And After

Previous studies have shown that the inhibition of renin secretion by vasopressin (AVP) in conscious dogs is related to vasoconstrictor activity and may be a reflex response mediated by the renal nerves. The aim of the present experiments was to determine whether the suppression of plasma renin activity (PRA) by AVP is blocked by renal denervation. AVP and, for comparison, angiotensin II (ANG II) were infused intravenously for 45 min in seven conscious dogs before and after bilateral renal denervation. Before denervation, AVP infusion at 0.2 and 1.0 ng X kg-1 X min-1 suppressed PRA from 7.4 +/- 1.1 to 4.7 +/- 1.0 (P less than 0.01) and from 7.9 +/- 1.8 to 3.8 +/- 0.8 ng X ml-1 X 3 h-1 (P less than 0.01), respectively. ANG II infusion at 5.0 and 10.0 ng X kg-1 X min-1 decreased PRA from 7.5 +/- 2.3 to 2.5 +/- 0.7 (P less than 0.01) and from 6.0 +/- 1.1 to 1.8 +/- 0.4 ng X ml-1 X 3 h-1 (P less than 0.01), respectively. One to three weeks following renal denervation, PRA had decreased from 6.7 +/- 1.3 to 2.9 +/- 0.5 ng X ml-1 X 3 h-1 (P less than 0.01), and renal norepinephrine was undetectable. After denervation, neither AVP infusion at 0.2 (3.0 +/- 0.5 to 2.4 +/- 0.4 ng X ml-1 X 3 h-1) nor 1.0 ng X kg-1 X min-1 (3.1 +/- 0.8 to 2.8 +/- 1.0 ng X ml-1 X 3 h-1) suppressed PRA.(ABSTRACT TRUNCATED AT 250 WORDS)

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