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Objective: Reno-renal reflexes are disturbed in cardiovascular and hypertensive conditions when elevated levels of pro-inflammatory mediators/cytokines are present within the kidney. We hypothesised that exogenously administered inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin (IL)-1β modulate the renal sympatho-excitatory response to chemical stimulation of renal pelvic sensory nerves., Methods: In anaesthetised rats, intrarenal pelvic infusions of vehicle [0.9% sodium chloride (NaCl)], TNF-α (500 and 1000 ng/kg) and IL-1β (1000 ng/kg) were maintained for 30 min before chemical activation of renal pelvic sensory receptors was performed using randomized intrarenal pelvic infusions of hypertonic NaCl, potassium chloride (KCl), bradykinin, adenosine and capsaicin., Results: The increase in renal sympathetic nerve activity (RSNA) in response to intrarenal pelvic hypertonic NaCl was enhanced during intrapelvic TNF-α (1000 ng/kg) and IL-1β infusions by almost 800% above vehicle with minimal changes in mean arterial pressure (MAP) and heart rate (HR). Similarly, the RSNA response to intrarenal pelvic adenosine in the presence of TNF-α (500 ng/kg), but not IL-1β, was almost 200% above vehicle but neither MAP nor HR were changed. There was a blunted sympatho-excitatory response to intrapelvic bradykinin in the presence of TNF-α (1000 ng/kg), but not IL-1β, by almost 80% below vehicle, again without effect on either MAP or HR., Conclusion: The renal sympatho-excitatory response to renal pelvic chemoreceptor stimulation is modulated by exogenous TNF-α and IL-1β. This suggests that inflammatory mediators within the kidney can play a significant role in modulating the renal afferent nerve-mediated sympatho-excitatory response., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This study examined the effect of leptin and orexin-A on autonomic baroreflex control in conscious Wistar rats exposed to high-fat (45% fat) or normal (3.4%) diet for 4 weeks. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were monitored during the generation of baroreflex gain curves and acute volume expansion (VEP). Intracerebroventricular (ICV) leptin (1 μg/min) increased RSNA in the normal diet group (0.31 ± 0.04 vs 0.23 ± 0.03 mV/s) and MAP in the high-fat diet group (115 ± 5 vs 105 ± 5 mm Hg, P < .05). Orexin-A (50 ng/min) increased RSNA, HR and MAP in the high-fat diet group (0.26 ± 0.03 vs 0.22 ± 0.02 mV/s, 454 ± 8 vs 417 ± 12 beats/min, 117 ± 1 vs 108 ± 1 mm Hg) and the normal diet group (0.18 ± 0.05 vs 0.17 ± 0.05 mV/s, 465 ± 10 vs 426 ± 6 beats/min, 116 ± 2 vs 104 ± 3 mm Hg). Baroreflex sensitivity for RSNA was increased during ICV leptin by 50% in the normal diet group, compared to 14% in the high-fat diet group (P < .05). Similarly, orexin-A increased baroreflex sensitivity by 56% and 50% in the high-fat and normal diet groups, respectively (all P < .05). During ICV saline, VEP decreased RSNA by 31 ± 5% (P < .05) after 10 minutes and the magnitude of this response was blunted during ICV infusion of leptin (17 ± 2%, P < .05) but not orexin-A in the normal diet group. RSNA response to VEP was not changed during ICV leptin or orexin-A in the high-fat diet group. These findings indicate possible central roles for leptin and orexin-A in modulating the baroreflexes under normal or increased fat intake in conscious rats and potential therapeutic approaches for obesity associated hypertension., (© 2020 John Wiley & Sons Australia, Ltd.)

New Findings: What is the central question of this study? Does immunosuppression restore the baroreflex control of renal sympathetic nerve activity (RSNA) in an animal model of kidney injury? What is the main finding and its importance? Tacrolimus, a calcineurin inhibitor, restored the high- and low-pressure baroreflex control of RSNA following cisplatin-induced renal injury., Abstract: Cisplatin administration causes depression of renal haemodynamic and excretory function and is associated with renal sympatho-excitation and loss of baroreflex regulation of renal sympathetic nerve activity (RSNA). This study investigated whether administration of the immunosuppressant tacrolimus in this cisplatin-mediated renal injury model could restore, or the acute intra-renal infusion of tumour necrosis factor α (TNF-α) could blunt, the high- or low-pressure baroreflex control of RSNA. Groups of control and cisplatin-treated (5 mg kg -1 , i.p. on day 0) rats received either saline or tacrolimus (0.25 mg kg -1  day -1 , i.p.) for 7 days prior to study. Rats were anaesthetised and prepared for measurement of mean arterial pressure (MAP), heart rate (HR) and RSNA. Baroreflex gain curves were generated and the degree of renal sympatho-inhibition determined (area under the curve (AUC) reported as %RSNA min) during acute volume expansion. Intrarenal TNF-α infusion (0.3 µg kg -1  h -1 ) in control rats decreased baroreflex gain by 32% (P < 0.05) compared to intra-renal saline infusion. In the cisplatin group (MAP: 98 ± 14 mmHg; HR: 391 ± 24beats min -1 ), the baroreflex gain for RSNA was 39% (P < 0.05) lower than that for the control group (MAP: 91 ± 7 mmHg; HR: 382 ± 29 beats min -1 ). In cisplatin-treated rats given daily tacrolimus (MAP: 84 ± 12 mmHg; HR: 357 ± 30 beats min -1 ), the baroreflex gain and renal sympatho-inhibition (AUC, 2440 ± 1071 vs. 635 ± 498% min) were restored to normal values. These findings provide evidence for the view that cisplatin administration initiates an injury involving inflammation which may contribute to the deranged baroreflex regulation of RSNA. This phenomenon appears mediated in part via the renal innervation., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

New Findings: What is the topic of this review? Reports that bilateral renal denervation in resistant hypertensive patients results in a long-lasting reduction in blood pressure raise the question of the underlying mechanisms involved and how they may be deranged in pathophysiological states of hypertension and renal failure. What advances does it highlight? The renal sensory afferent nerves and efferent sympathetic nerves work together to exert an important control over extracellular fluid volume, hence the level at which blood pressure is set. This article emphasizes that both the afferent and the efferent renal innervation may contribute to the neural dysregulation of the kidney that occurs in chronic renal disease and resistant hypertension. Autonomic control is central to cardiovascular homeostasis, and this is exerted not only at the level of the heart and blood vessels but also at the kidney. At the kidney, the sympathetic neural regulation of renin release and fluid reabsorption may influence fluid balance and, in the longer term, the level at which blood pressure is set. The role of the renal innervation in the regulation of blood pressure has received renewed attention over the past few years, following the reports that bilateral renal denervation of resistant hypertensive patients resulted in a marked reduction in blood pressure, which has been maintained for several years. Such has been the interest that this approach of renal denervation is being applied in other patient groups with diabetes, obesity and renal failure, with the hope that there may be a sustained reduction in blood pressure as well as the amelioration of some aspects of the metabolic syndrome. However, the factors that come into play to cause the rise in blood pressure in these patient groups, particularly the resistant hypertensive patients, are far from clear. Moreover, the mechanisms leading to the fall in blood pressure following renal denervation of resistant hypertensive patients currently elude our understanding and is therefore an area that requires much more investigation to enhance our insight.

Objectives: This study investigated the hypothesis that angiotensin II (type 2) (AT2) receptor activation to modulate the renal sympatho-inhibition to saline volume expansion was dependent on nitric oxide production., Methods: Renal sympatho-inhibition to a saline volume expansion (VEP, 0.25% body weight/min i.v. for 30 min) was studied following intracerebroventricular (ICV) saline, CGP42112 (CGP, AT2 agonist), PD123319 (AT2 antagonist), and losartan (AT1 antagonist), and then in combination with N-nitro-L-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor)., Results: ICV saline, PD123319, CGP, and losartan did not change baseline mean arterial pressure, heart rate, or renal sympathetic nerve activity (RSNA). VEP decreased RSNA in all groups by 58-62% (P<0.05). CGP enhanced the decrease in RSNA compared to saline (74 vs. 60%; P<0.05), whereas PD123319 was without effect (58 vs. 57%). L-NAME only increased baseline RSNA when co-administered with PD123319 (P<0.05). VEP-induced reduction in RSNA following L-NAME was less than during ICV saline (46 vs. 62%; P<0.05). In the group where PD123319 preceded L-NAME, the fall in RSNA was smaller than when PD123319 was infused alone (40 vs. 63%; P<0.05), but not if PD123319 followed L-NAME (52 vs. 44%). L-NAME did not change the magnitude of VEP-induced sympatho-inhibition following CGP (67 vs. 60%). Losartan enhanced the renal sympatho-inhibition to VEP (70 vs. 62%; P<0.05), the magnitude of which was unchanged when L-NAME was present (70 vs. 65%)., Conclusion: AT2 receptor activation enhances the VEP-induced reduction in RSNA. Although nitric oxide is important in allowing the normal renal sympatho-inhibitory response to VEP, this is not dependent on AT2 receptors.

Background: It remains unclear whether Shiga toxin-2 (Stx-2)-induced acute encephalopathy contributes to an inappropriate activation of the renal sympathetic outflow. This investigation set out to examine the impact of Stx-2 administered into the brain on the neural control of the kidney., Methods: Using acutely anaesthetised male Wistar rats (300-350 g), saline, Stx-2 (10 μg/kg) or lipopolysaccharide (LPS 50 μg/kg) was administered intracerebroventricularly (icv) and measurements of renal haemodynamic and excretory function or renal nerve activity were made over the following 4 h., Results: There were minimal changes in renal blood flow, glomerular filtration rate, urine flow or sodium excretion, irrespective of whether saline, Stx-2 or LPS was administered into the brain. The renal nerve recordings showed that whereas saline and LPS caused small inconsistent changes in renal nerve activity over the 4-h period, there was a significant (P < 0.05) doubling of renal nerve activity in the rats which were administered Stx-2 icv. Immunocytochemical examination demonstrated that Stx-2 induced globotriaosylceramide receptors, the proposed functional receptors for Stx-2, on the blood vessel walls around the hypothalamus and hippocampus, and histological evaluations showed that changes in the kidney were beginning to occur to the renal tubular epithelial cells, consistent with developing lesions., Conclusion: Stx-2 crosses either the blood-brain barrier or the blood-cerebrospinal fluid barrier where it can alter neuronal function and trigger neuronal derangements. These structural changes could contribute, at least in part, to the raised renal sympathetic nerve activity.

There is evidence that in cardiac failure, there is defective baroreceptor reflex control of sympathetic nerve activity. Often, cardiac failure is preceded by a state of cardiac hypertrophy in which there may be enhanced performance of the heart. This study investigated whether in two different models of cardiac hypertrophy, there was an increased contribution of nitric oxide (NO) to the low-pressure baroreceptor regulation of renal sympathetic nerve activity (RSNA) and nerve-dependent excretory function. Administration of a volume load, 0.25* body wt/min saline for 30 min, in normal rats decreased RSNA by 40* and increased urine flow by some 9-fold. Following nitro-L-arginine methyl ester (L-NAME) administration, 10 μg·kg(-1)·min(-1) for 60 min, which had no effect on blood pressure, heart rate, or RSNA, the volume load-induced renal sympathoinhibitory and excretory responses were markedly enhanced. In cardiac hypertrophy states induced by 2 wk of isoprenaline/caffeine or 1 wk thyroxine administration, the volume challenge failed to suppress RSNA, and there were blunted increases in urine flow in the innervated kidneys, but following L-NAME infusion, the volume load decreased RSNA by 30-40* and increased urine flow by some 20-fold in the innervated kidneys, roughly to the same extent as observed in normal rats. These findings suggest that the blunted renal sympathoinhibition and nerve-dependent diuresis to the volume load in cardiac hypertrophy are related to a heightened production or activity of NO within either the afferent or central arms of the reflex.

Objective: Excessive dietary Na intake can enhance the autonomic control of blood pressure, but the physiological mechanisms are unclear. This study examined how low (0.03%) and high (3.0%) dietary Na intake, from weaning (4 weeks) to adulthood (11 weeks), altered the pressor and renal sympathoexcitatory responses to peripheral and spinal V1 receptor activation., Methods: Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were monitored in α-chloralose/urethane anaesthetized male Wistar rats., Results: Dose-dependent increases in MAP were observed in all groups to intravenous (i.v.) vasopressin [arginine vasopressin (AVP); 1-10 ng 0.2 ml] and phenylephrine (1-10 μg 0.2 ml), and in the high Na group, these responses were enhanced but to a greater extent for AVP than phenylephrine (P<0.001). A direct dose-dependent rise in RSNA to intrathecal (10 μl) AVP (1-100 μmol/l) and glutamate (10-100 mmol/l) was observed in the normal Na group. The RSNA responses were enhanced in the high Na group at lower doses of intrathecal AVP (1 μmol/l, P<0.01; 5 μmol/l, P<0.05) and all doses of glutamate (P<0.001) compared to the normal Na group. In the low Na group, the RSNA responses to intrathecal AVP were suppressed, but those to intrathecal glutamate were enhanced compared to normal Na (P<0.001) and similar to the high Na group., Conclusion: These data demonstrated that high Na enhanced peripheral and spinal V1-mediated responses. Interestingly, low Na intake blunted the spinal V1-mediated RSNA responses, but sensitized those to spinal glutamate, which may be a compensatory mechanism to ensure adequate neural control of the kidney when dietary Na intake is reduced., (© 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins)

Background: This study examined the effect of renal sympathetic innervation on adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction in Wistar-Kyoto (WKY) rats., Methods: Forty-eight WKY rats were treated with either losartan (10 mg/kg/day p.o.) or carvedilol (5 mg/kg/day p.o.) or a combination of them (10 mg/kg/day + 5 mg/kg/day p.o.) for 7 days. On day 8, the rats were anaesthetized, and renal vasoconstrictor experiments were carried out. A group of rats was subjected to acute unilateral renal denervation during the acute study. Changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by Ang II, noradrenaline (NA), and methoxamine (ME)., Results: In normal animals, losartan decreased (P < 0.05) the renal vasoconstrictor response to Ang II but not to NA or ME. Carvedilol treatment, however, blunted (P < 0.05) the renal vasoconstrictor responses to Ang II and adrenergic agonists. Combination of losartan and carvedilol blunted (P < 0.05) the renal vasoconstrictor response to Ang II but augmented the responses to NA and ME (all P < 0.05). Interestingly, when denervated rats were treated with the same combination, there was a reduction (P < 0.05) in the renal vasoconstrictor responses to Ang II and adrenergic agonists., Conclusions: Data suggest that the renal sympathetic nerve contributes to adrenergic agonist-mediated renal vasoconstrictions in normal rats. The data further indicate an interactive relationship between renin-angiotensin and sympathetic nervous systems in modulating adrenergically and Ang II-induced renal vasoconstriction in WKY rats.

Aim: We assessed the role of renal sympathetic nervous system in the deterioration of renal hemodynamic and excretory functions in rats with streptozotocin (STZ)-induced diabetic kidney disease (DKD)., Methods: Male Sprague-Dawley (SD) rats were induced with diabetes mellitus (DM) using STZ (55 mg/kg, i.p.). The acute studies were conducted on denervated anesthetized rats 7 days after STZ administration. Two sets of experiments were performed: clearance experiments in which six 20-min urine and plasma collections were carried out to measure kidney function parameters, and hemodynamic experiments in which the renal nerves were electrically stimulated and responses in renal vascular resistance (RVR) and renal blood flow (RBF) were recorded., Results: Renal denervation in STZ-induced diabetic rats produced higher fractional excretion of sodium (FE(Na) ) but lower plasma sodium (P(Na) ), glomerular filtration rate (GFR), and plasma creatinine (P(Cr) ) (all P<0.05 vs. innervated diabetic rats). In innervated diabetic rats, renal nerve stimulation (RNS) caused significant attenuation in the renal vasoconstrictor responses (all P<0.05 vs. innervated control). Renal denervation in diabetic rats significantly blunted these responses (all P<0.05 vs. innervated diabetic rats); however, they were significantly higher (all P<0.05) while compared to denervated control counterparts., Conclusions: The data demonstrate an early role for the renal sympathetic innervation in the pathogenesis of DKD. If the kidney is prevented from renal sympathetic nerve action renal functional parameters are markedly improved. The data further suggest an early enhancement in renal sensitivity to intrarenal norepinephrine (NE) upon the removal of renal sympathetic tone in STZ-induced diabetic rats., (Copyright © 2011 Wiley-Liss, Inc.)

Background: Renal sympathetic innervation plays an important role in the control of renal hemodynamics and may therefore contribute to the pathophysiology of many disease states affecting the kidney. Thus, the present study aimed to investigate the role of the renal sympathetic nervous system in the early deteriorations of renal hemodynamics and structure in rats with pathophysiological states of renal impairment., Methods: Anesthetized Sprague Dawley (SD) rats with cisplatin-induced acute renal failure (ARF) or streptozotocin (STZ)-induced diabetes mellitus (DM) were subjected to a renal hemodynamic study 7 days after cisplatin and STZ administration. During the acute study, renal nerves were electrically stimulated, and responses in renal blood flow (RBF) and renal vascular resistance (RVR) were recorded in the presence and absence of renal denervation. Post mortem kidney collection was performed for histopathological assessment., Results: In innervated ARF or DM rats, renal nerve stimulation produced significantly lower (all p<0.05, vs. innervated control) renal vasoconstrictor responses. These responses were markedly abolished when renal denervation was performed (all p<0.05); however, they appeared significantly higher compared with denervated controls (all p<0.05). Kidney injury was suppressed in denervated ARF, while, irrespective of renal denervation, renal specimens from DM rats were comparable to controls., Conclusions: Renal sympathoexcitation is involved in the pathogenesis of the renal impairment accompanying ARF and DM, and may even precede the establishment of an observable renal injury. There is a possible enhancement in the renal sensitivity to intrarenal norepinephrine following renal denervation in ARF and DM rats.

Background: It is well established that renal sympathetic nerves are primarily involved in renal sodium and water regulation. However, the relationship between renal sympathetic nerve activity (RSNA) and renal potassium handling is not extensively known. The present study was performed to investigate the role of the renal sympathetic nervous system in the regulation of tubular potassium reabsorption and secretion., Methods: Male Sprague Dawley (SD) rats (each group, n=6) were fasted overnight, anesthetized with pentobarbital sodium (60 mg/kg intraperitoneal), denervated by application of phenol to the left renal artery and maintained on an intravenous infusion of saline for 2 hours. During this period, 6 urine and plasma samples were collected at 20-minute intervals to study kidney function parameters., Results: In denervated rats, there were significantly higher (all p<0.05 vs. innervated control) urine flow rate (UFR), glomerular filtration rate (GFR), absolute sodium excretion (U(Na)V), fractional sodium excretion (FE(N)a), absolute potassium excretion (U(K)V), fractional potassium excretion (FE(K)) and urinary sodium to urinary potassium ratio (U(Na)/U(K)). No appreciable differences were seen in the mean arterial pressure (MAP) and plasma sodium (P(Na)) between denervated and innervated SD rats. However, plasma potassium (P(K)) levels were significantly lower (p<0.05) in denervated rats as compared with innervated counterparts., Conclusions: There is a possible involvement of renal nerves in the regulation of renal potassium handling. This effect is largely attributable to a direct action of renal sympathetic nerves on the renal tubular segments.

Aim: We investigated the role of renal sympathetic innervation in the deterioration of renal haemodynamic and excretory functions during the early post-ischaemic phase of renal ischaemia/reperfusion injury., Methods: Anaesthetised male Sprague-Dawley rats were subjected to unilateral renal ischaemia by clamping the left renal artery for 30 min followed by reperfusion. Following acute renal denervation clearance experiments were performed. In a different set of experiments, the renal nerves were electrically stimulated at increasing frequencies and responses in renal blood flow and renal vascular resistance were recorded., Results: Denervated post-ischaemic acute renal failure (ARF) rats showed higher urine flow rate, absolute and fractional sodium excretions, urinary sodium to urinary potassium, glomerular filtration rate and basal renal blood flow but lower basal renal vascular resistance (all p < 0.05 vs innervated ARF rats). Potassium excretion was significantly lower in denervated group as per fractional (p < 0.05 vs innervated ARF rats) but not absolute potassium excretion (p > 0.05 vs innervated ARF rats). The rise in mean arterial pressure and renal vasoconstrictor response to renal nerve stimulation were blunted in denervated ischaemic ARF rats (all p < 0.05 vs innervated ARF rats). Renal histopathology in denervated ARF rats manifested a significantly lower medullary congestion, inflammation and tubular injury compared to innervated counterparts (p < 0.05 vs innervated ARF rats)., Conclusions: The findings strongly suggest the involvement of renal sympathetic tone in the post-ischaemic events of ischaemic ARF, as the removal of its action to a degree ameliorated the post-ischaemic renal dysfunctions.

The regulation of blood pressure and sympathetic outflow by the brain renin-angiotensin system in animals subjected to raised or lowered dietary Na(+) intake is unclear. This study compared the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to intracerebroventricular (i.c.v.) infusion of angiotensin II (AngII) and III (AngIII) before and after peripheral V(1) receptor blockade (V(1)B) in alpha-chloralose-urethane-anaesthetized rats fed a low (0.03%, LNa(+)), normal (0.3%, NNa(+)) or high Na(+) diet (3.0%, HNa(+)) from 4 to 11 weeks of age. The rise in MAP 2 min post AngII i.c.v. was greater in HNa(+) (14 +/- 3 mmHg) versus LNa(+) (8 +/- 1 mmHg, P < 0.05) and after AngIII i.c.v. in HNa(+) (14 +/- 3 mmHg) versus NNa(+) (6 +/- 1 mmHg, P < 0.05) and LNa(+) (7 +/- 1 mmHg, P < 0.05). The MAP responses to AngII and AngIII i.c.v. were abolished after V(1)B in LNa(+), but were only attenuated in HNa(+). In NNa(+), V(1)B blunted the MAP responses to AngII and abolished those to AngIII. The MAP remained elevated 30 min after AngII in all groups, but returned to baseline levels 15 min after AngIII in NNa(+) and HNa(+) (P < 0.01). Twenty minutes after i.c.v. AngII, RSNA rose above baseline in HNa(+) (112 +/- 1%), a response not observed in the LNa(+) and NNa(+) groups. Twenty minutes post AngIII i.c.v., RSNA was elevated in both HNa (109 +/- 2%) and NNa(+) (109 +/- 2%). After V(1)B, RSNA rose only in the HNa(+) group 15 min post AngIII infusion (109 +/- 1%). Together, these findings: (1) suggest that HNa(+) intake augments the MAP and RSNA responses to i.c.v. AngII and AngIII; (2) highlight an important role for peripheral V(1) receptors during these responses; and (3) differentiate the effects of AngII and AngIII on blood pressure and RSNA.

The role of renal sympathetic nerves in the pathogenesis of ischemic acute renal failure (ARF) and the immediate changes in the renal excretory functions following renal ischemia were investigated. Two groups of male Sprague Dawley (SD) rats were anesthetized (pentobarbitone sodium, 60 mg kg(-1) i.p.) and subjected to unilateral renal ischemia by clamping the left renal artery for 30 min followed by reperfusion. In group 1, the renal nerves were electrically stimulated and the responses in the renal blood flow (RBF) and renal vascular resistance (RVR) were recorded, while group 2 was used to study the early changes in the renal functions following renal ischemia. In post-ischemic animals, basal RBF and the renal vasoconstrictor reperfusion to renal nerve stimulation (RNS) were significantly lower (all p < 0.05 vs. control). Mean arterial pressure (MAP), basal RVR, urine flow rate (UFR), absolute and fractional excretions of sodium (U(Na)V and FE(Na)), and potassium (U(K)V and FE(K)) were higher in ARF rats (all p < 0.05 vs. control). Post-ischemic animals showed markedly lower glomerular filtration rate (GFR) (p < 0.05 vs. control). No appreciable differences were observed in urinary sodium to potassium ratio (U(Na)/U(K)) during the early reperfusion phase of renal ischemia (p > 0.05 vs. control). The data suggest an immediate involvement of renal sympathetic nerve action in the pathogenesis of ischemic ARF primarily through altered renal hemodynamics. Diuresis, natriuresis, and kaliuresis due to impaired renal tubular functions are typical responses to renal ischemia and of comparable magnitudes.

This study aimed to quantify the effect of cardiac hypertrophy induced with isoprenaline and caffeine on reflex regulation of renal sympathetic nerve activity by the arterial and cardiopulmonary baroreceptors. Male Wistar rats, untreated or given water containing caffeine and subcutaneous (s.c.) isoprenaline every 72 h for 2 weeks or thyroxine s.c. for 7 days, were anaesthetized and prepared for measurement of renal sympathetic nerve activity or cardiac indices. Both isoprenaline-caffeine and thyroxine treatment blunted weight gain but increased heart weight and heart weight to body weight ratio by 40 and 14% (both P<0.01), respectively. In the isoprenaline-caffeine group, the maximal rate of change of left ventricular pressure and the contractility index were higher by 17 and 14% (both P<0.01), respectively, compared with untreated rats. In the isoprenaline-caffeine-treated rats, baroreflex gain curve sensitivity was depressed by approximately 30% (P<0/05), while the mid-point blood pressure was lower, by 15% (P<0/05), and the range of the curve was 60% (P<0.05) greater than in the untreated rats. An acute intravenous infusion of a saline load decreased renal sympathetic nerve activity by 42% (P<0.05) in the untreated rats but had no effect in the isoprenaline-caffeine- or the thyroxine-treated groups. The isoprenaline-caffeine treatment induced cardiac hypertrophy with raised cardiac performance and an associated depression in the reflex regulation of renal sympathetic nerve activity by both high- and low-pressure baroreceptors. The thyroxine-induced cardiac hypertrophy also blunted the low-pressure baroreceptor-mediated renal sympatho-inhibition. These findings demonstrate that in cardiac hypertrophy without impaired cardiac function, there is a blunted baroreceptor control of renal sympathetic outflow.

In this study we employed both detrended fluctuation analysis (DFA) and multiscale entropy (MSE) measurements to compare the long-range temporal correlation (LRTC) of multifibre renal sympathetic nerve activity (RSNA) between conscious and anesthetized Wistar rats. It was found that both methods showed the obvious LRTC properties in conscious state. Moreover, the scaling exponent of the RSNA in conscious rats was significantly higher than that in anesthetized rats. The results of MSE analysis showed that the entropy values, derived from the conscious group, increased on small time scales and then stabilized to a relatively constant value whereas the entropy measure, derived from anesthetized animals, almost monotonically decreased. This suggests that the fractal properties of underlying dynamics of the system have been reduced by anesthesia. The results demonstrate that apparently random fluctuations in multifibre RSNA are dictated by a complex deterministic process that imparts "long-term" memory to the dynamic system. However, this memory is significantly weakened by anesthesia.

It was hypothesized that renal sympathetic nerve activity (RSNA) and neuronal nitric oxide synthase (nNOS) are involved in the acute inhibition of renin secretion and the natriuresis following slow NaCl loading (NaLoad) and that RSNA participates in the regulation of arterial blood pressure (MABP). This was tested by NaLoad after chronic renal denervation with and without inhibition of nNOS by S-methyl-thiocitrulline (SMTC). In addition, the acute effects of renal denervation on MABP and sodium balance were assessed. Rats were investigated in the conscious, catheterized state, in metabolic cages, and acutely during anesthesia. NaLoad was performed over 2 h by intravenous infusion of hypertonic solution (50 micromol.min(-1).kg body mass(-1)) at constant body volume conditions. SMTC was coinfused in amounts (20 microg.min(-1).kg(-1)) reported to selectively inhibit nNOS. Directly measured MABPs of acutely and chronically denervated rats were less than control (15% and 9%, respectively, P < 0.005). Plasma renin concentration (PRC) was reduced by renal denervation (14.5 +/- 0.2 vs. 19.3 +/- 1.3 mIU/l, P < 0.005) and by nNOS inhibition (12.4 +/- 2.3 vs. 19.6 +/- 1.6 mlU/l, P < 0.005). NaLoad reduced PRC (P < 0.05) and elevated MABP modestly (P < 0.05) and increased sodium excretion six-fold, irrespective of renal denervation and SMTC. The metabolic data demonstrated that renal denervation lowered sodium balance during the first days after denervation (P < 0.001). These data show that renal denervation decreases MABP and renin secretion. However, neither renal denervation nor nNOS inhibition affects either the renin down-regulation or the natriuretic response to acute sodium loading. Acute sodium-driven renin regulation seems independent of RSNA and nNOS under the present conditions.

Angiotensin II receptor density in the brain is elevated when dietary salt intake is raised or in the state of hypertension. The aim of this study was to evaluate whether the angiotensin II modulation of the baroreceptor control of renal sympathetic nerve activity was altered under these conditions. Wistar rats, fed either a regular (0.25% w/w sodium) or high-salt diet (3.1% w/w sodium), or stroke-prone spontaneously hypertensive rats (SHRSPs) were implanted with cannulae in the carotid artery, jugular vein and the cerebroventricle and with recording electrodes on the renal sympathetic nerves. Three days later, baroreceptor gain curves were generated for renal sympathetic nerve activity and heart rate before and following intracerebroventricular (i.c.v.) administration of losartan (15 mug) to block angiotensin AT1 receptors. The rats fed a regular diet had a mean blood pressure of 116 +/- 3 mmHg and heart rate of 467 +/- 25 beats min(-1), which remained unchanged after the i.c.v. administration of losartan. The sensitivity or curvature coefficient of the baroreceptor curve for renal sympathetic nerve activity was increased by 36% (P < 0.05) following losartan. In the rats fed a high-salt diet, all cardiovascular variables and the losartan-induced increase in the baroreceptor curvature coefficient for renal sympathetic nerve activity (29%) were similar to values in rats on the regular sodium diet. The heart rate baroreceptor curvature coefficient was not altered in either the rats fed a regular or a high-salt diet. The slope of the renal sympathetic nerve activity baroreflex gain curve in the SHRSPs was less and the increase following administration of losartan (54%) was greater than in the Wistar rats. These data indicate that in the conscious state, the tonic inhibitory action of brain angiotensin II on the baroreflex regulation of renal sympathetic nerve activity was unaffected by raised dietary sodium, but its role was enhanced in the SHRSPs.

Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3-4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. [ABSTRACT FROM AUTHOR]

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This paper explores the possible relationships between dietary fructose and altered neurohumoral regulation of renal haemodynamic and excretory function in this model of metabolic syndrome. Fructose consumption induces hyperinsulinemia, hypertriglyceridaemia, insulin resistance, and hypertension. The pathogenesis of fructose-induced hypertension is dubious and involves numerous pathways acting both singly and together. In addition, hyperinsulinemia and hypertension contribute significantly to progressive renal disease in fructose-fed rats. Moreover, increased activity of the renin-angiotensin and sympathetic nervous systems leading to downregulation of receptors may be responsible for the blunted vascular sensitivity to angiotensin II and catecholamines, respectively. Various approaches have been suggested to prevent the development of fructose-induced hypertension and/or metabolic alteration. In this paper, we address the role played by the renin-angiotensin and sympathetic nervous systems in the haemodynamic alterations that occur due to prolonged consumption of fructose. [ABSTRACT FROM AUTHOR]

1 The study investigated whether endothelin (ET) contributed to the diabetes-associated alterations in volume reflex and characterised the receptor subtype that might be involved. The influence of renal sympathetic nerves on these aspects of ET was also examined. 2 Groups of nondiabetic and streptozotocin-induced diabetic rats were subjected to an acute isotonic saline volume expansion (VE), 10% body wt in the presence and absence of ET antagonists. 3 Cumulative urine sodium excretion (CuN[SUBNa]V) after VE in diabetic rats reached values of 116±10 in the denervated and 74±6μmolmin[SUP-1]g kidney wt[SUP-1] in the innervated kidneys, which were both less (both P&lt0.001) than those achieved in the nondiabetic rats, at 267±9 in the denervated and 183±10 μmolmin[SUP-1] g kidney wt[SUP-1] in the innervated kidney, respectively. 4 Diabetic rats pretreated with a nonselective Et[SUBA]/ET[SUBB] antagonist had an enhanced CuN[SUBNa] V in the denervated kidneys by 37% (P<0.01) compared to that of untreated diabetic rats. At both does of SB 209670 these increments were less than the values obtained previously in nondiabetic rats (both P<0.01). The ET[SUBA]/ET[SUBB] antagonist had no meaningful effect on CuN[SUBNa]V in the innervated kidneys of the diabetic rats, whereas previous studies in nondiabetic rats showed the response to be depressed. The Cu Na[SUBNa]V responses to VE in diabetic rats given the selective ET[SUBA] antagonist were not different from those observed in untreated diabetic rats, irrespective of whetehr or not the renal nerves were present. IN nondiabetic rats, the ET[SUBA] antagonist had an action similar to the mixed antagonist. 5 These findings demonstrate that activation of ET[SUBB] receptors contributes to the depressed ability to excrete a saline load in diabetes mellitus, but its impact is obscured by the influence of the renal nerves. [ABSTRACT FROM AUTHOR]

ANGII infused ICV in rats on a normal Na+ (NNa+) diet leads to a pressor response and a fall in renal sympathetic nerve activity (RSNA) while rats fed a high Na+ (HNa+) diet also express a later rise in RSNA. This study investigated the impact of peripheral V1 receptor blockade (V1B) on these responses. Male Wistar rats fed a NNa+ (0.3% Na+) or HNa+ (3.0%, Na+) diet for 6 weeks were anaesthetized, cannulae inserted into the femoral artery/vein and right ICV and RSNA recorded from the left kidney. Blood pressure (BP) and RSNA were measured after ICV ANGII (50-100ng in 2µL; NNa+ n=7-10) and during V1 blockade (V1B, Manning compound, 10µg/0.2mL IV; n=6). Data (mean±SE) were compared by ANOVA. P<0.05 indicated significance. Basal BP (mmHg) was similar between groups (ANGII: NNa+ 89±4, HNa+ 95±4; ANGII + V1B: NNa+ 89±4 , HNa+84±4). The 30 min area under the curve (AUC) BP response (ΔmmHg*min) was less during V1B in NNa+ (ANGII: 232±47 vs ANGII+ V1B: 60±29, P<0.05) and HNa+ (ANGII: 237±66 vs ANGII+ V1B: 73±i3, P<0.05). RSNA fell immediately after ICV ANGII in NNa+ (ANGII: 94±3%, ANGII+ V1B: 94±2, P<0.05) and HNa+ (ANGII: 84±6%, ANGII + V1: 91±3%, P<0.05 vs baseline) with no effect of V1B. The rise in RSNA in the HNa+rats 30 min after ICV ANGII was not present during V1B (ANGII:112±2%, ANGII + V1B: 96±6%, P<0.05). The results suggest that V1 receptor activation contributes to the BP and long term rise in RSNA to ICV ANGII. [ABSTRACT FROM AUTHOR]

This study determined the impact of AT1 receptor antisense ODN given icv on the baroreflex control of RSNA in conscious rats. Male Wistar and SHR (n=5-6) were chronically instrumented with cannulae in the femoral artery and jugular vein, electrodes sealed onto the left renal nerve and a cannula implanted into the right lateral cerebroventricle. Three days later, blood pressure (BP) was manipulated by iv phenylephrine and nitroprusside (both at 10µg) to generate baroreflex curves for RSNA (Huang et al 2006, J Physiol 574: 597-604) before and 1 day after the icy administration of 25µg AT1 receptor antisense ODN or 25µg sense ODN dissolved in 20µl lipofectin (1 µg/µl). Means ±SEM were subjected to Student's t test and significance taken at P<0.05. In Wistar rats, BP was 115±5mmHg and was unchanged after the ATI receptor antisense ODN, but there was a significant (P<0.05) increase in the sensitivity of the baroreflex curve of 86.0%. BP in the SHR, at 172±5mmHg, was decreased after the antisense ODN to 148±6mmHg (P<0.05), while the sensitivity of the baroreflex curve increased by 55.1% (P<0.05). Administration of the sense ODN had no effect on BP or the baroreflex curves in either Wistar or SHR. The data showed that whereas the ATI receptor antisense ODN decreased BP only in the SHR, it increased the sensitivity of the baroreflex control of RSNA in both conscious Wistar and SHR. [ABSTRACT FROM AUTHOR]