Role of renal nerves in sodium retention of cirrhosis and congestive heart failure

1991 ◽  
Vol 260 (2) ◽  
pp. R298-R305 ◽  
Author(s):  
G. F. DiBona ◽  
L. L. Sawin
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Renal Denervation ◽  
Bile Duct Ligation ◽  
Renal Nerves ◽  
Coronary Artery Ligation ◽  
Common Bile Duct Ligation ◽  
Artery Ligation ◽  
Duct Ligation

To define the role of renal nerves in renal Na retention of cirrhosis and congestive heart failure (CHF), experiments were done in rats with cirrhosis due to common bile duct ligation (CBDL) and CHF due to myocardial infarction from left coronary artery ligation. Two weeks after induction of CBDL or CHF, diseased and sham diseased (Sham) rats were subjected to bilateral renal denervation (DNX) or sham renal denervation (innervated, INN). Five days after DNX or INN, 26-day metabolic balance studies were carried out in all rats. Daily dietary Na intake averaged 2.0-3.0 meq/day on days 1-6 and 22-26 and averaged 0.120 meq/day on days 7-21. Cumulative Na balance was greater in CBDL and CHF rats, INN or DNX, than in Sham/CBDL or CHF rats throughout the study. On day 6 at the end of the normal dietary Na intake period (days 0-6), cumulative Na balance was not affected by renal denervation in Sham/CBDL or CHF rats (INN, 2.02 +/- 0.19 meq, n = 10; DNX, 2.04 +/- 0.17 meq, n = 11), CBDL rats (INN, 4.21 +/- 0.39 meq, n = 10; DNX, 3.78 +/- 0.37 meq, n = 10), or CHF rats (INN, 3.74 +/- 0.72 meq, n = 9; DNX, 3.22 +/- 0.55 meq, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of ETA receptors in the regulation of vascular reactivity in rats with congestive heart failure

2000 ◽  
Vol 279 (2) ◽  
pp. H844-H851 ◽  
Author(s):  
Eric Thorin ◽  
Martin Lucas ◽  
Peter Cernacek ◽  
Jocelyn Dupuis
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Smooth Muscle ◽  
Vascular Reactivity ◽  
Cerebral Arteries ◽  
No Synthase ◽  
Cerebrovascular Reactivity ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Endothelial Denudation

Endothelium-derived nitric oxide (NO) and endothelin (ET)-1 interact to regulate vascular tone. In congestive heart failure (CHF), the release and/or the activity of both factors is affected. We hypothesized that the increased ET-1 production associated with CHF may result in a reduced smooth muscle sensitivity to NO. The aim of this study was to evaluate the effects of a chronic treatment with the ETA-receptor (ET receptor A) antagonist LU-135252 (LU) on cerebrovascular reactivity to sodium nitroprusside (SNP) in the rat infarct model of CHF. Rats were subjected to coronary artery ligation and were treated for 4 wk with placebo ( n = 24) or LU (50 mg · kg−1 · day−1, n = 29). CHF was associated with a decreased ( P < 0.05) efficacy of SNP to induce relaxation of isolated middle cerebral arteries. Furthermore, neither NO synthase inhibition with N ω-nitro-l-arginine (l-NNA) nor endothelial denudation affected the efficacy of SNP. Thus the endothelium no longer influences smooth muscle sensitivity to SNP. LU treatment, however, normalized ( P < 0.05) smooth muscle sensitivity to SNP. Sensitivity of ET-1-induced contraction was increased in CHF only in the presence of l-NNA, whereas contraction induced by ETB receptor (receptor B) stimulation was increased ( P < 0.05) in endothelium-denuded vessels. LU treatment restored these changes in reactivity and revealed a significant endothelium-dependent ETB-mediated relaxation after NO synthase inhibition. In conclusion, CHF decreases and uncouples cerebrovascular smooth muscle sensitivity to SNP from endothelial regulation. The observation that chronic ETAblockade restored most of the changes associated with CHF suggests that activation of the ET-1 system importantly contributes to the alteration in vascular reactivity observed in experimental CHF.

New insights into the pathological role of TNF-α in early cardiac dysfunction and subsequent heart failure after infarction in rats

2004 ◽  
Vol 287 (1) ◽  
pp. H340-H350 ◽  
Author(s):  
C. Berthonneche ◽  
T. Sulpice ◽  
F. Boucher ◽  
L. Gouraud ◽  
J. de Leiris ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Diastolic Pressure ◽  
Subsequent Development ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Direct Role ◽  
Volume Curve ◽  
Tnf Α

A marked increase in plasma TNF-α has been described in patients with chronic heart failure (CHF). Nevertheless, little is known about the direct role of this cytokine early after myocardial infarction (MI) and its possible effects on the subsequent development of CHF. Wistar rats were subjected to permanent in vivo coronary artery ligation. At 5, 7, and 9 days after MI, cardiac function, passive compliance of the left ventricle (LV), and cardiac geometry were evaluated. The same model was used to perform pharmacological studies 7 days and 10 wk after MI in rats treated with monomeric recombinant human soluble TNF-α receptor type II (sTNF-RII, 40 μg/kg iv) or a placebo on day 3. Maximal alterations of cardiac function and geometry occurred 7 days after MI, which correlated chronologically with a peak of cardiac and serum TNF-α, as shown by immunohistochemistry and ELISA, respectively. sTNF-RII improved LV end-diastolic pressure under basal conditions and after volume overload 7 days and 10 wk after MI. Moreover, a significant leftward shift of the pressure-volume curve in the sTNF-RII-treated group 7 days after MI indicated a preservation of LV volume. Infarct expansion index was also significantly improved by sTNF-RII 7 days after MI ( P < 0.01). Nevertheless, 10 wk after MI, geometric indexes and passive pressure-volume curves were not significantly improved by the treatment. In conclusion, TNF-α plays a major role in cardiac alterations 7 days after MI in rats and contributes to hemodynamic derangement, but not to cardiac remodeling, in subsequent CHF.

Abstract 17163: Prolonged Increase in Endothelium-Specific NOX2-Derived Cytosolic Oxidants Exacerbates Maladaptive Cardiac Remodeling in Ischemic Myocardium

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Rayane Brinck Teixeira ◽  
Melissa Pfeiffer ◽  
Catherine Karbasiafshar ◽  
Frank W Sellke ◽  
Ruhul Abid
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Left Ventricle ◽  
Wall Thickness ◽  
Molecular Mechanisms ◽  
Prolonged Exposure ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Left Ventricle Mass

Introduction: Global increase in reactive oxygen species (ROS) in endothelial cells (EC) plays major roles in cardiovascular disease (CVD). However, the precise role of ROS within specific compartments of ECs are not yet known. This study aims to address the role of endothelium-derived cytosolic ROS in myocardial infarction (MI). Hypothesis: We hypothesized that an extended exposure to increased NADPH oxidase 2 (NOX2)-derived cytosolic ROS in EC would result in a worse post-MI outcome. Methods: Binary conditional transgenic mice expressing NOX2 in an EC-specific manner (NOX2VE) were studied. NOX2VE mice were assigned to tetracycline (Tet)-ON (control) to turn off transgene, or without Tet as Tet-OFF, i.e. NOX2- O ver E xpressing (NOX2VE-OE) groups. After 15 weeks of Tet-ON/OFF treatment, all mice were subjected to left anterior descending (LAD) coronary artery ligation that mimics acute MI (n=10/group). Left ventricle function was assessed by echocardiography 28 days post LAD. Ejection fraction (EF), fractional shortening (FS), left ventricle mass, wall thickness, heart rate, chamber diameter and volume at systole and diastole were analyzed by Student’s t-test. Results: Echocardiographic data showed that mice subjected to an increased NOX2-derived ROS in EC (NOX2VE-OE) presented with 19.3 ± 7.7% and 20.8 ± 7.9% decrease in EF and FS, respectively (p<0.05) compared to control (NOX2VE, Tet-ON). NOX2VE-OE mice showed an increase (by 14.1 ± 3.4%, p<0.01) in diastolic posterior wall thickness (DPWT) suggesting ventricular stiffness. NOX2VE-OE group also showed increased cardiac mass (by 14.0 ± 5.4%, p<0.05), which, along with DPWT indicates hypertrophy with a likelihood to develop heart failure. Interestingly, heart rate, systolic and diastolic chamber volume and diameters, stroke volume, and cardiac output showed no differences between the groups (p>0.05). Conclusions: Together, these results suggest that prolonged exposure to increased cytosolic ROS in coronary EC results in worse cardiac performance and myocardial stiffness, leading to a higher propensity to heart failure after MI. Currently, in vivo signaling studies are being carried out to understand molecular mechanisms by which NOX2-derived ROS in ECs result in impaired cardiac function.

Chronic blockade of brain "ouabain" prevents sympathetic hyper-reactivity and impairment of acute baroreflex resetting in rats with congestive heart failure

1999 ◽  
Vol 78 (1) ◽  
pp. 45-53
Author(s):  
Bing S Huang ◽  
Baoxue Yuan ◽  
Frans HH Leenen
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Congestive Heart Failure ◽  
Venous Pressure ◽  
Control Group ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Sympathetic Hyperactivity ◽  
Air Jet ◽  
Baroreflex Function

In rats with congestive heart failure (CHF) post myocardial infarction (MI) acute blockade of brain "ouabain" reverses sympathetic hyperactivity and chronic blockade prevents the desensitization of baroreflex function. This study was conducted to determine: i) if chronic blockade of brain "ouabain" maintains normal sympathetic reactivity; andii) if acute baroreflex resetting (another parameter of baroreflex function) also becomes impaired, and if so, does brain "ouabain" contribute to impairment in acute baroreflex resetting. CHF post MI was induced by acute coronary artery ligation in Wistar rats. Animals were treated with 200 µg·day-1 i.c.v. or i.v. Fab fragments (which bind brain "ouabain" with high affinity), or treated with 200 µg·day-1 i.c.v. gamma-globulins (control group). The length of treatment was 0.5-8 weeks or 4-8 weeks post MI. At 8 weeks mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were recorded in concious rats at rest and in response to: i) air-jet stress, ii) i.c.v. guanabenz (an α2-adrenoceptor agonist), and iii) a 30 min i.v. infusion of nitroprusside (NP). Excitatory responses to air stress and inhibitory responses to guanabenz of MAP, HR, and RSNA were significantly enhanced in rats with CHF versus the sham-operated treated group. This enhancement was prevented in the CHF group treated with i.c.v., but not i.v., Fab. Nitroprusside induced a sustained decrease in MAP (~ 25 mmHg) and a transient decrease in CVP. Heart rate and RSNA increased significantly within 1 min of beginning the infusion. The peak increases as well as the product of changes in MAP-HR and RSNA-HR were significantly smaller in rats with CHF treated with gamma-globulins versus sham rats and versus CHF rats treated with i.c.v. Fab. In sham-operated rats and CHF rats treated with i.c.v. Fab, RSNA and HR began to decrease within 3-4 min of beginning the NP infusion and had returned to baseline by 20 min. In contrast, RSNA and HR remained increased throughout the infusion in the CHF rats treated with gamma-globulins. These data indicate that in rats with CHF acute resetting of the arterial baroreflex in response to a lower BP becomes impaired, and chronic blockade of brain "ouabain" prevents both this change in baroreflex resetting as well as sympathetic hyperactivity.Key words: heart failure, acute baroreflex resetting, sympathetic hyperactivity, nitroprusside.

scholarly journals Renal denervation improves sodium excretion in rats with chronic heart failure: effects on expression of renal ENaC and AQP2

2019 ◽  
Vol 317 (5) ◽  
pp. H958-H968 ◽  
Author(s):  
Hong Zheng ◽  
Xuefei Liu ◽  
Kenichi Katsurada ◽  
Kaushik P. Patel
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Sodium Channels ◽  
Renal Denervation ◽  
Water Retention ◽  
Renal Cortex ◽  
Renal Nerves ◽  
Coronary Artery Ligation ◽  
Epithelial Sodium Channels ◽  
Aquaporin 2

Previously we have shown that increased expression of renal epithelial sodium channels (ENaC) may contribute to the renal sodium and water retention observed during chronic heart failure (CHF). The goal of this study was to examine whether renal denervation (RDN) changed the expressions of renal sodium transporters ENaC, sodium-hydrogen exchanger-3 proteins (NHE3), and water channel aquaporin 2 (AQP2) in rats with CHF. CHF was produced by left coronary artery ligation in rats. Four weeks after ligation surgery, surgical bilateral RDN was performed. The expression of ENaC, NHE3, and AQP2 in both renal cortex and medulla were measured. As a functional test for ENaC activation, diuretic and natriuretic responses to ENaC inhibitor benzamil were monitored in four groups of rats (Sham, Sham+RDN, CHF, CHF+RDN). Western blot analysis indicated that RDN (1 wk later) significantly reduced protein levels of α-ENaC, β-ENaC, γ-ENaC, and AQP2 in the renal cortex of CHF rats. RDN had no significant effects on the protein expression of kidney NHE3 in both Sham and CHF rats. Immunofluorescence studies of kidney sections confirmed the reduced signaling of ENaC and AQP2 in the CHF+RDN rats compared with the CHF rats. There were increases in diuretic and natriuretic responses to ENaC inhibitor benzamil in rats with CHF. RDN reduced the diuretic and natriuretic responses to benzamil in CHF rats. These findings suggest a critical role for renal nerves in the enhanced expression of ENaC and AQP2 and subsequent pathophysiology of renal sodium and water retention associated with CHF. NEW & NOTEWORTHY This is the first study to show in a comprehensive way that renal denervation initiated after a period of chronic heart failure reduces the expression of epithelial sodium channels and aquaporin 2 leading to reduced epithelial sodium channel function and sodium retention.

Normal contractions triggered by I Ca,L in ventricular myocytes from rats with postinfarction CHF

2002 ◽  
Vol 283 (3) ◽  
pp. H1225-H1236 ◽  
Author(s):  
Ivar Sjaastad ◽  
Janny Bøkenes ◽  
Fredrik Swift ◽  
J. Andrew Wasserstrom ◽  
Ole M. Sejersted
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Coronary Artery ◽  
Sarcoplasmic Reticulum ◽  
Ventricular Myocytes ◽  
Cardiac Contractility ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Fractional Shortening

Attenuated L-type Ca2+ current ( I Ca,L), or current-contraction gain have been proposed to explain impaired cardiac contractility in congestive heart failure (CHF). Six weeks after coronary artery ligation, which induced CHF, left ventricular myocytes from isoflurane-anesthetized rats were current or voltage clamped from −70 mV. In both cases, contraction and contractility were attenuated in CHF cells compared with cells from sham-operated rats when cells were only minimally dialyzed using high-resistance microelectrodes. With patch pipettes, cell dialysis caused attenuation of contractions in sham cells, but not CHF cells. Stepping from −50 mV, the following variables were not different between sham and CHF, respectively: peak I Ca,L (4.5 ± 0.3 vs. 3.8 ± 0.3 pApF−1 at 23°C and 9.4 ± 0.5 vs. 8.4 ± 0.5 pApF−1 at 37°C), the bell-shaped voltage-contraction relationship in Cs+ solutions (fractional shortening, 15.2 ± 1.0% vs. 14.3 ± 0.7%, respectively, at 23°C and 7.5 ± 0.4% vs. 6.7 ± 0.5% at 37°C) and the sigmoidal voltage-contraction relationship in K+ solutions. Caffeine-induced Ca2+ release and sarcoplasmic reticulum Ca2+-ATPase-to-phospholamban ratio were not different. Thus CHF contractions triggered by I Ca,L were normal, and the contractile deficit was only seen in undialyzed cardiomyocytes stimulated from −70 mV.

Abstract 652: Coronary Capillaries in Ischemic Congestive Heart Failure in Rats Exhibit Significant Morphological Disorder

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Heather J Kagan ◽  
Jiqiu Chen ◽  
Peter Backeris ◽  
Irene C Turnbull ◽  
Kevin D Costa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Ischemia Reperfusion Injury ◽  
Morphological Changes ◽  
Ischemia Reperfusion ◽  
Circular Statistics ◽  
Coronary Artery Ligation ◽  
Sem Images ◽  
Artery Ligation ◽  
Ischemic Congestive Heart Failure

In ischemic congestive heart failure (CHF), the heart is damaged and undergoes compensatory remodeling, a pathological process associated with harmful effects. The goal of this study is to explore the manifestation of CHF by examining the morphological changes occurring in the coronary microvasculature in CHF versus normal rat hearts. We tested the hypothesis that coronary capillaries in rats with CHF exhibit significantly more morphological disorder than those in control rats. Methods: CHF was induced by aortic banding, ischemia/reperfusion injury two months post-banding (left coronary artery ligation for 30 minutes) and aortic debanding one month post-injury. Resin polymer containing fluorescent dye was injected into coronary vasculature of excised hearts. Muscle tissue was digested using NaOH to reveal vascular casts that were sputter coated with gold for imaging under a Scanning Electron Microscope (SEM). A total of 93 SEM images from 14 rats (7 control, 7 CHF) were analyzed for structural alignment using an automated gradient detection algorithm and circular statistics implemented using MATLAB software; Mean Vector Length (MVL) was calculated for each image as a measure of capillary organization (0<MVL<0. MVL->1 perfect alignment, MVL->0 random disarray). Results: CHF capillaries exhibit significantly more structural disorder than control (MVL 0.35±0.02 for 61 CHF, 0.58±0.02 for 32 control. p<0.01). Conclusions: Coronary capillaries in CHF rats exhibit significant abnormal morphological disarray that may impair blood flow hemodynamics and material and oxygen exchange in myocytes. Such disordered capillary remodeling could have detrimental consequences for the progression and prognosis of heart failure.

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