Abstract P220: Congestive Heart Failure in the Rat Induces Subtle Renal Damage via Neurogenic Pathways

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Tilmann Ditting ◽  
Peter Linz ◽  
Martin Hindermann ◽  
Kristina Rodionova ◽  
Sonja Heinlein ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Structural Damage ◽  
Collagen I ◽  
Renal Nerves ◽  
Nodose Ganglion Neurons ◽  
Ganglion Neurons ◽  
Cardiac Afferents ◽  
And Control ◽  
Renal Sympathetic

Background: Cardiomyopathy in experimental renal insufficiency is putatively influenced by neurogenic pathways of renal origin. We wondered if cardiac neurogenic effects in congestive heart failure could likewise harm the kidney. We hypothesized that increased renal sympathetic nerve activity (RSNA) in rats with congestive heart failure after myocardial infarction (CHF) induces renal structural damage. Methods: 21 day after induction of CHF renal morphology was evaluated by immunohistology (interstitial and glomerular mononuclear cell infiltration (ED1), cell proliferation (PCNA), collagen I,III,IV,V,VI, laminin und fibronectin). RSNA was assessed by volume challenge (VE) to decrease RSNA. CHF and control rats were investigated with and without renal denervation (DNX). Blood pressure (BP), heart rate (HR) and RSNA were recorded. Nodose ganglion neurons (NGN) with vagal cardiac afferents were cultured for 1 day. Whole cell recordings were obtained and current-voltage relationships established. Cells were characterized by osmomechanical stress with a mannitol solution. Results: In CHF rats with intact renal nerves (nonDNX) formation of collagen I occurred, that was reduced after DNX (12.2+0.7 %area vs. 9.1+1.1 %area*, n=6, * p<0.05). VE-induced RSNA decreases were impaired in CHF vs controls suggesting increased RSNA (-α 34+8% vs. -α[[Unable to Display Character: &#61472;]]54+6% *, n=6, * p<0.05). NGN from CHF exhibited altered conductance in response to mechanical stress as compared to controls (change in holding current at -80 mV: control_normoosmotic: -144±30 pA; control_hypoos.: -282±34 pA vs CHF_normosmotic: - 230±55 pA; CHF_hypos.: -540±100* pA; *p<0.05 CHF vs. control). Conclusion: CHF induced subtle renal structural damage due to increased renal sympathetic tone which was likely due to altered NGN mechanosensitivity. Afferent nerve units from cardiovascular organs obviously form a complex sympathomodulatory network.

scholarly journals Angiotensin receptor antagonist improves cardiac reflex control of renal sodium handling in heart failure

1998 ◽  
Vol 274 (2) ◽  
pp. H636-H641 ◽  
Author(s):  
Gerald F. Dibona ◽  
Susan Y. Jones ◽  
Linda L. Sawin
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Right Atrial ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Renal Sodium Handling ◽  
Renal Sympathetic

In rats with congestive heart failure, type 1 angiotensin II receptor antagonist treatment (losartan) decreases basal renal sympathetic nerve activity and improves arterial baroreflex regulation of renal sympathetic nerve activity. This investigation examined the effect of losartan on cardiac baroreflex regulation of renal sympathetic nerve activity and renal sodium handling in rats with congestive heart failure. Losartan treatment decreased arterial pressure from 120 ± 3 to 93 ± 5 mmHg and increased the afferent (from 0.95 ± 0.21 to 2.22 ± 0.42% Δafferent vagal nerve activity/mmHg mean right atrial pressure, P < 0.05) and overall gain (from −1.14 ± 0.19 to −4.20 ± 0.39% Δrenal sympathetic nerve activity/mmHg mean right atrial pressure, P < 0.05) of the cardiac baroreflex. During isotonic saline volume loading, urinary sodium excretion increased from 2.4 ± 0.8 to 10.5 ± 1.3 μeq/min in vehicle-treated rats (excretion of 52 ± 3% of the load) and from 3.0 ± 1.0 to 15.1 ± 1.8 μeq/min in losartan-treated rats (excretion of 65 ± 4% of the load, P < 0.05). When rats were changed from a low- to a high-sodium diet, cumulative sodium balance over 5 days was 7.8 ± 0.6 meq in vehicle-treated rats and 4.2 ± 0.4 meq in losartan-treated rats ( P < 0.05). In congestive heart failure, losartan treatment improved cardiac baroreflex regulation of renal sympathetic nerve activity, which was associated with improved ability to excrete acute and chronic sodium loads.

Enhanced Expression and Function of Renal SGLT2 (Sodium-Glucose Cotransporter 2) in Heart Failure: Role of Renal Nerves

2021 ◽  
Author(s):  
Kenichi Katsurada ◽  
Shyam S. Nandi ◽  
Neeru M. Sharma ◽  
Kaushik P. Patel
Keyword(s):  
Heart Failure ◽  
Clinical Studies ◽  
Sglt2 Inhibitor ◽  
Renal Nerves ◽  
Coronary Artery Ligation ◽  
Functional Responses ◽  
Sodium Glucose Cotransporter ◽  
And Function ◽  
Renal Sympathetic

Background: Recent clinical studies demonstrate that SGLT2 (sodium-glucose cotransporter 2) inhibitors ameliorate heart failure (HF). The present study was conducted to assess the expression and function of renal SGLT2 and the influence of enhanced renal sympathetic tone in HF. Methods: Four weeks after coronary artery ligation surgery to induce HF, surgical bilateral renal denervation (RDN) was performed in rats. Four groups of rats (Sham-operated control [Sham], Sham+RDN, HF and HF+RDN; n=6/group) were used. Immunohistochemistry and Western blot analysis were performed to evaluate the renal SGLT2 expression. One week after RDN (5 weeks after induction of HF), intravenous injection of SGLT2 inhibitor dapagliflozin were performed to assess renal excretory responses. In vitro, human embryonic kidney cells were used to investigate the fractionation of SGLT2 after norepinephrine treatment. Results: In rats with HF, (1) SGLT2 expression in the proximal tubule of the kidney was increased; (2) the response of increases in urine flow, sodium excretion, and glucose excretion to dapagliflozin were greater; and (3) RDN attenuated renal SGLT2 expression and normalized renal functional responses to dapagliflozin. In vitro, norepinephrine promoted translocation of SGLT2 to the cell membrane. Conclusions: These results indicate that the enhanced tonic renal sympathetic nerve activation in HF increases the expression and functional activity of renal SGLT2. Potentiated trafficking of SGLT2 to cell surface in renal proximal tubules mediated by norepinephrine may contribute to this functional activation of SGLT2 in HF. These findings provide critical insight into the underlying mechanisms for the beneficial effects of SGLT2 inhibitors on HF reported in the clinical studies.

Renal effects of brain natriuretic peptide in patients with congestive heart failure

1999 ◽  
Vol 96 (1) ◽  
pp. 5-15 ◽  
Author(s):  
Kaare T. JENSEN ◽  
Hans EISKJÆR ◽  
Jan CARSTENS ◽  
Erling B. PEDERSEN
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Healthy Subjects ◽  
Renal Plasma Flow ◽  
Urinary Flow ◽  
Absolute Increase ◽  
Control Subjects ◽  
And Control

The effect of a continuous infusion of human brain natriuretic peptide, 2 ;pmol·min-1·kg-1, during 60 ;min was studied in nine patients with congestive heart failure and in 10 healthy control subjects. Brain natriuretic peptide increased from 1.6 to 101 ;pmol/l in control subjects and from 25 to 173 ;pmol/l in congestive heart failure during infusion. Urinary sodium excretion increased significantly in both congestive heart failure (60%) and control subjects (71%), but the absolute increase was significantly lower in congestive heart failure (27 ;μmol/min) than in control subjects (190 ;μmol/min). Urinary flow rate did not change. The lithium clearance technique was used to evaluate the segmental tubular function; the distal fractional reabsorption of sodium decreased significantly less in congestive heart failure (DFRNa: -0.8%) than in control subjects (DFRNa: -3.7%). Baseline values for glomerular filtration rate and renal plasma flow were reduced in congestive heart failure, but brain natriuretic peptide induced no significant changes between congestive heart failure and control subjects. Brain natriuretic peptide induced the same absolute increase in secondary messenger cGMP in plasma and urine in both patients and healthy subjects. It is concluded that the natriuretic response to brain natriuretic peptide infusion was impaired in patients with congestive heart failure compared with healthy subjects, and it is likely that the impaired natriuretic response was caused by a reduced responsiveness in the distal part of the nephron.

Altered responsiveness of the kidney to activation of the renal nerves in fat-fed rabbits

2009 ◽  
Vol 296 (6) ◽  
pp. R1889-R1896 ◽  
Author(s):  
Sylvia Michaels ◽  
Gabriela A. Eppel ◽  
Sandra L. Burke ◽  
Geoffrey A. Head ◽  
James Armitage ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Neural Control ◽  
Control Diet ◽  
Plasma Renin ◽  
Sympathetic Nerves ◽  
Urine Flow ◽  
Renal Nerves ◽  
Renal Nerve ◽  
And Control ◽  
Renal Sympathetic

We tested whether mild adiposity alters responsiveness of the kidney to activation of the renal sympathetic nerves. After rabbits were fed a high-fat or control diet for 9 wk, responses to reflex activation of renal sympathetic nerve activity (RSNA) with hypoxia and electrical stimulation of the renal nerves (RNS) were examined under pentobarbital anesthesia. Fat pad mass and body weight were, respectively, 74% and 6% greater in fat-fed rabbits than controls. RNS produced frequency-dependent reductions in renal blood flow, cortical and medullary perfusion, glomerular filtration rate, urine flow, and sodium excretion and increased renal plasma renin activity (PRA) overflow. Responses of sodium excretion and medullary perfusion were significantly enhanced by fat feeding. For example, 1 Hz RNS reduced sodium excretion by 79 ± 4% in fat-fed rabbits and 46 ± 13% in controls. RNS (2 Hz) reduced medullary perfusion by 38 ± 11% in fat-fed rabbits and 9 ± 4% in controls. Hypoxia doubled RSNA, increased renal PRA overflow and medullary perfusion, and reduced urine flow and sodium excretion, without significantly altering mean arterial pressure (MAP) or cortical perfusion. These effects were indistinguishable in fat-fed and control rabbits. Neither MAP nor PRA were significantly greater in conscious fat-fed than control rabbits. These observations suggest that mild excess adiposity can augment the antinatriuretic response to renal nerve activation by RNS, possibly through altered neural control of medullary perfusion. Thus, sodium retention in obesity might be driven not only by increased RSNA, but also by increased responsiveness of the kidney to RSNA.

Reduced NO enhances the central gain of cardiac sympathetic afferent reflex in dogs with heart failure

1999 ◽  
Vol 276 (1) ◽  
pp. H19-H26 ◽  
Author(s):  
Rong Ma ◽  
Irving H. Zucker ◽  
Wei Wang
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Heart Rate ◽  
Congestive Heart Failure ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Cardiac Sympathetic Afferent Reflex ◽  
Renal Sympathetic ◽  
Stimulation Of

The aim of the present study was to test the hypothesis that a decrease in central nitric oxide (NO) is involved in the enhancement of the central gain of the cardiac “sympathetic afferent” reflex (CSAR) in dogs with congestive heart failure (CHF). Thirteen dogs with pacing-induced CHF and sixteen sham dogs were anesthetized with α-chloralose and were baroreceptor denervated and vagotomized. The CSAR was evoked by stimulation of the left ventral ansa. A lateral cerebroventricular cannula was inserted to deliver sodium nitroprusside (SNP) and N G-nitro-l-arginine methyl ester (l-NAME). Arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) were recorded at baseline and during elicitation of the CSAR. We found that 1) the responses of RSNA to stimulation were augmented in dogs with CHF, 2) SNP depressed the increase in RSNA induced by the CSAR in CHF dogs but had no effect in sham dogs, and 3)l-NAME potentiated the CSAR-induced increase in RSNA in sham dogs but not in dogs with CHF. We conclude that reduced central NO is involved in the enhanced central gain of the CSAR in CHF dogs.

Role of renal nerves in control of sodium excretion in chronic congestive heart failure

1989 ◽  
Vol 256 (6) ◽  
pp. F1084-F1093 ◽  
Author(s):  
H. L. Mizelle ◽  
J. E. Hall ◽  
J. P. Montani
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Sodium Excretion ◽  
Sodium Intake ◽  
Left Kidney ◽  
Renal Nerves ◽  
Chronic Congestive Heart Failure ◽  
Control Mechanisms ◽  
Sodium Retention ◽  
Ventricular Pacing

The aim of this study was to examine the contribution of the renal nerves to the sodium retention in chronic congestive heart failure produced by rapid ventricular pacing. In 10 female dogs the left kidney was denervated and the urinary bladder was split to allow separate 24-h urine collection from an innervated and a denervated kidney in the same dog. The dogs were placed on an 80-meq/day sodium intake and permitted to recover for at least 2 wk. Control measurements were made for 5 days followed by ventricular pacing at 270-300 beats/min for 6 days. Cardiac output (CO), measured with an electromagnetic flow probe around the ascending aorta, fell from a control of 2.4 +/- 0.3 to 1.4 +/- 0.2 l/min (6 day average) during pacing while mean arterial pressure (MAP) fell from 91 +/- 4 to 71 +/- 3 mmHg. In six dogs, sodium excretion fell to an average of less than 2 meq/day (80 meq/day intake) during the 6-day pacing period in both the innervated and denervated kidneys. In four dogs, sodium excretion returned back toward control on days 3-6 of pacing despite sustained reductions in CO and MAP. However, there were no differences in renal hemodynamics or electrolyte excretion between innervated and denervated kidneys in either the compensated or decompensated dogs. These results suggest that other control mechanisms, besides the renal nerves, are primarily responsible for the sodium retention in this model of chronic congestive heart failure.

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