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.

High-NaCl diets increase natriuretic and diuretic responses in salt-resistant but not salt-sensitive SHR

1991 ◽  
Vol 260 (6) ◽  
pp. F890-F897 ◽  
Author(s):  
M. S. Mozaffari ◽  
S. Jirakulsomchok ◽  
Z. H. Shao ◽  
J. M. Wyss
Keyword(s):  
Arterial Pressure ◽  
Renal Denervation ◽  
Isotonic Saline ◽  
Renal Nerves ◽  
Sprague Dawley ◽  
Volume Loading ◽  
Spontaneously Hypertensive ◽  
Volume Load ◽  
Sprague Dawley Rats ◽  
Wistar Kyoto

This study tested the hypothesis that NaCl-sensitive spontaneously hypertensive rats (SHR-S) display a defect in natriuretic and diuretic responses to acute volume loading that contributes to the rise in arterial pressure observed when the rats are fed a high-NaCl diet. Seven-week-old SHR-S and NaCl-resistant SHR rats (SHR-R) and normotensive (Wistar-Kyoto and Sprague-Dawley rats) were fed high- or basal NaCl diets. After 2.5 wk on the diets, preinstrumented conscious rats received an intravenous infusion (5% body wt; 0.5 ml/min) of isotonic saline, and urine was collected through a bladder catheter for 90 min. Control rats on the high-NaCl diet (compared with basal) excreted a significantly greater percentage of Na+ and volume load. In contrast, SHR-S on high-NaCl diet (compared with basal) had a very small increase in natriuretic response and no increase in diuretic response to volume expansion. The effect of renal denervation on natriuretic and diuretic responses to volume load was tested. In SHR-R on 1 and 8% NaCl diets, renal denervation had little or no effect on these responses, suggesting that renal nerves do not play a prominent role in the dietary NaCl-induced increases in the natriuretic and diuretic responses to volume load. These results demonstrate that NaCl-resistant rats rapidly adapt to diets high in NaCl content with increased natriuretic and diuretic responses to acute volume loading. The failure of SHR-S to adapt to the dietary challenge may result in volume loading and a secondary increase in arterial pressure after feeding.

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.

Role of renal nerves in onset and maintenance of spontaneous hypertension

1982 ◽  
Vol 243 (2) ◽  
pp. H284-H288 ◽  
Author(s):  
R. A. Norman ◽  
D. J. Dzielak
Keyword(s):  
Arterial Pressure ◽  
Renal Denervation ◽  
Indirect Measurement ◽  
Renal Nerves ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Norepinephrine Content ◽  
Wistar Kyoto

Renal denervation has been reported to delay development of hypertension in Okamoto spontaneously hypertensive rats (SHR) but to have no effect on the final hypertensive state. However, functional reinnervation begins to occur about 1 mo after renal denervation. The arterial pressure of SHR undergoing repeated bilateral renal denervations at the age of 4, 7, 10, 13, and 16 wk was compared with that in sham-operated SHR. In addition, the effect of successive renal denervations at 4, 7, and 10 wk of age in Wistar-Kyoto (WKY) control rats was determined. Both indirect measurement of pressure by the tail-cuff technique and mean arterial pressure (MAP) measurement indicated that renal denervation prevents full expression of hypertension in SHR. MAP in 19-wk-old renal-denervation SHR averaged 159 +/- 5.1 mmHg (SE) vs. 178 +/-0 4.2 mmHg in sham-operated SHR. Renal denervation had no effect on arterial pressure of WKY rats. Renal norepinephrine content in the renal-denervated WKY rats and SHR was less than 20% of that in the sham-operated groups. Successive bilateral renal denervations every 3 wk blocks 30-40% of the expected progressive elevation of arterial pressure in aging SHR.

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.

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.

Effect of acute renal denervation and ANF on renal function in adult spontaneously hypertensive rats

1991 ◽  
Vol 261 (4) ◽  
pp. R835-R841
Author(s):  
D. M. Pollock ◽  
W. J. Arendshorst
Keyword(s):  
Renal Function ◽  
Spontaneously Hypertensive Rats ◽  
Renal Denervation ◽  
Renal Nerves ◽  
Hypertensive Rats ◽  
Water Excretion ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Fractional Excretion Of Sodium ◽  
Shr And Wky Rats

Experiments were designed to evaluate the influence of the renal efferent nerves on baseline renal function and on the renal response to atrial natriuretic factor (ANF) in euvolemic anesthetized 10- to 12-wk-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) and Munich-Wistar (MW) rats. Acute unilateral renal denervation produced increases in absolute and fractional excretion of sodium and water by the ipsilateral kidney that were similar in SHR and WKY rats; larger responses were observed in MW rats. Excretion by the contralateral innervated kidney was unchanged in each group. Intravenous infusion of ANF (0.25 microgram.kg-1.min-1) caused a diuresis and natriuresis that was similar in the three strains and independent of changes in glomerular filtration rate and renal blood flow. The excretory responses to ANF were larger in denervated than in innervated kidneys. The magnitude of the natriuresis and diuresis produced by ANF was directly related to the pre-ANF rate of urinary excretion, suggesting independent and additive effects of acute renal denervation and ANF on tubular reabsorption. The exaggerated response in the acutely denervated kidney can be explained by removal of a modulatory effect of the renal efferent nerves and associated increases in tubular flow and delivery to more distal ANF-sensitive sites. The denervation responses suggest that the renal efferent nerves have similar effects on sodium and water reabsorption in anesthetized SHR and WKY rats at 10-12 wk of age. The renal nerves and ANF appear to play a larger role in the acute control of sodium and water excretion in MW rats compared to rats of the Okamoto-Aoki strain.

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.

Effects of High Salt Intake and Meclofenamate on Arterial Pressure and Renal Function in the Spontaneously Hypertensive Rat

1979 ◽  
Vol 57 (s5) ◽  
pp. 251s-253s ◽  
Author(s):  
S. G. Chrysant
Keyword(s):  
Renal Function ◽  
Arterial Pressure ◽  
Sodium Intake ◽  
Left Ventricular ◽  
Spontaneously Hypertensive ◽  
High Sodium ◽  
High Sodium Intake ◽  
High Salt Intake ◽  
Group 2 ◽  
Group 1

1. The effects of prolonged high sodium intake (duration 3 months) and meclofenamate were studied in two groups of male spontaneously hypertensive (SH) rats. 2. Group 1 (eight rats) received 1% NaCl in water and served as controls, and group 2 received 1% NaCl in water plus meclofenamate (3·5–4·0 mg daily). 3. Group 2 rats developed higher arterial pressure, renal vascular resistance and left ventricular weight and greater renal histological changes, with lower effective renal plasma flow, renal blood flow and glomerular filtration rate, than group 1. No differences were observed between the two groups in heart rate, body weight, fluid intake, urine volume, UNaV, UKV and right ventricular weight. 4. The results suggest that the combination of high sodium intake and meclofenamate exerts a greater damaging effect on the arterial pressure and renal function of SH rats than salt alone.

Effect of acute and chronic renal denervation on renal function after release of unilateral ureteral obstruction in the rat

1979 ◽  
Vol 57 (7) ◽  
pp. 731-737 ◽  
Author(s):  
D. R. Wilson ◽  
U. Honrath ◽  
M. Sole
Keyword(s):  
Renal Function ◽  
Ureteral Obstruction ◽  
Renal Denervation ◽  
Renal Plasma Flow ◽  
Unilateral Ureteral Obstruction ◽  
Urine Flow ◽  
Renal Nerves ◽  
Renal Nerve ◽  
Functional Changes ◽  
Anaesthetized Rats

The role of the renal nerves in determining renal function after relief of 24-h unilateral ureteral obstruction (UUO) was studied using clearance techniques in anaesthetized rats. Acute renal denervation during the first 1-2 h after relief of UUO resulted in a significant increase in glomerular filtration rate (GFR), renal plasma flow (RPF), urine flow, and sodium and potassium excretion, changes which were not seen in the sham-denervated postobstructive kidney. Acute denervation of sham-operated normal kidneys caused a similar natriuresis and diuresis but with no change in GFR or RPF. Chronic renal denervation 4-5 days before UUO resulted in no change in the function of the postobstructive kidney compared with sham-denervated postobstructive controls, while chronic denervation alone was associated with a significantly higher urine flow and sodium excretion rate from the denervated kidney. The effectiveness of renal denervation was confirmed by demonstrating marked depletion of tissue catecholamines in the denervated kidney.It was concluded that renal nerve activity plays a significant but not a major role in the functional changes present after relief of UUO. Chronic renal denervation did not protect against the functional effects of unilateral ureteral obstruction.

Neuronal regulation of renal function: A model system for nervous system interactions

1992 ◽  
Vol 70 (5) ◽  
pp. 733-734 ◽  
Author(s):  
J. Michael Wyss
Keyword(s):  
Nervous System ◽  
Renal Function ◽  
Renal Disease ◽  
Easy Access ◽  
Renal Nerves ◽  
Clinical Consequence ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Nerve Activity

The kidney is the most highly innervated peripheral organ, and both the excretory and endocrine functions of the kidney are regulated by renal nerve activity. The kidney plays a dominant role in body fluid homeostasis, blood ionic concentration, and pH and thereby contributes importantly to systemic blood pressure control. Early studies suggested that the neural-renal interactions were responsible only for short-term adjustments in renal function, but more recent studies indicate that the renal nerves may be a major contributor to chronic renal defects leading to established hypertension and (or) renal disease. The neural-renal interaction is also of considerable interest as a model to elucidate the interplay between the nervous system and peripheral organs, since there is abundant anatomical and physiological information characterizing the renal nerves. The investigator has easy access to the renal nerves and the neural influence on renal function is directly quantifiable both in vivo and in vitro. In this symposium that was presented at the 1990 annual convention of the Society for Neuroscience in St. Louis, Missouri, three prominent researchers evaluate the most recent progress in understanding the interplay between the nervous system and the kidney and explore how the results of these studies relate to the broader questions concerning the nervous system's interactions.First, Luciano Barajas examines the detailed anatomy of the intrarenal distribution of the efferent and afferent renal nerves along the nephron and vasculature, and he evaluates the physiological role of each of the discrete components of the innervation. His basic science orientation combined with his deep appreciation of the clinical consequence of the failure of neural-renal regulation enhances his discussion of the anatomy. Ulla C. Kopp discusses the role of the renorenal reflex, which alters renal responses following stimulation of the contralateral kidney. She also considers her recent findings that efferent renal nerve activity can directly modify sensory feedback to the spinal cord from the kidney. Finally, J. Michael Wyss examines the functional consequences of neural control of the kidney in health and disease. Although the nervous system has often been considered as only an acute regulator of visceral function, current studies into hypertension and renal disease suggest that neural-renal dysfunction may be an important contributor to chronic diseases.Together, these presentations examine most of the recent advances in the area of neural-renal interactions and point out how these data form a basis for future research into neuronal interactions with all visceral organs. The relative simplicity of the neural-renal interaction makes this system an important model with which to elucidate all neural-peripheral and neural-neural interactions.

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