Renal neurohormonal regulation in heart failure decompensation

Jönsson, Sofia; Becirovic‐Agic, Mediha; Narfström, Fredrik; Melville, Jacqueline; Hultström, Michael

doi:10.1152/ajpregu.00178.2014

Cited by 36 publications

(27 citation statements)

References 70 publications

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“…Increased renal sympathetic nerve stimulation is a major mechanism for salt and water retention in patients with circulatory failure 1, 41, 42 . Fluid retention in CHF, while necessary to increase preload and maintain cardiac output, leads to venous congestion and potentially decompensation 1, 43 . Our observations demonstrate that the activity of ANG II and AT 1 R in the PVN may play a substantial role in the sympathetic stimulation associated with CHF.…”

Section: Discussionmentioning

confidence: 99%

“…In chronic heart failure (CHF) increased sympathetic signaling exacerbates cardiac stress, both directly and by stimulating fluid retention by the kidneys through increased renal sympathetic nerve activity (RSNA) 1 , which is an important cause of morbidity and mortality 2, 3 . The paraventricular nucleus (PVN) participates in the regulation of sympathetic outflow 4-8 .…”

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confidence: 99%

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Sympathoexcitation in Rats With Chronic Heart Failure Depends on Homeobox D10 and MicroRNA-7b Inhibiting GABBR1 Translation in Paraventricular Nucleus

Wang

Huang

Zhou

et al. 2016

Circ: Heart Failure

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Background Chronic heart failure (CHF) increases sympathoexcitation through Angiotensin II (ANG II) receptors (AT1R) in the paraventricular nucleus (PVN). Recent publications indicate down regulation of γ-aminobutyric acid B-type receptor 1 (GABBR1) and has a binding site for microRNA-7b (miR-7b) that is expressed in the PVN. We hypothesized that ANG II regulates sympathoexcitation through homeobox D10 (HoxD10), which regulates miR-7b in other tissues. Methods and Results Ligation of the left anterior descendent coronary artery in rats caused CHF and sympathoexcitation. PVN expression of AT1R, HoxD10 and miR-7b was increased, while GABBR1 was lower in CHF. Infusion of miR-7b in the PVN caused sympathoexcitation in control animals, and enhanced the changes in CHF. Antisense miR-7b infused in PVN normalized GABBR1 expression while attenuating CHF symptoms including sympathoexcitation. A luciferase reporter assay detected miR-7b binding to the 3’-UTR of GABBR1 that was absent after targeted mutagenesis. ANG II induced HoxD10 and miR-7b in NG108 cells, effects blocked by AT1R-blocker losartan (Los) and by HoxD10 silencing. miR-7b transfection into NG108 cells decreased GABBR1 expression, which was inhibited by miR-7b antisense. In vivo PVN knockdown of AT1R attenuated the symptoms of CHF, while HoxD10 overexpression exaggerated them. Finally, in vivo PVN ANG II infusion caused dose dependent sympathoexcitation that was abrogated by miR-7b antisense and exaggerated by GABBR1 silencing. Conclusions There is an ANG II/AT1R/HoxD10/miR-7b/GABBR1 pathway in the PVN that contributes to sympathoexcitation and deterioration of cardiac function in CHF.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Sympathoexcitation in Rats With Chronic Heart Failure Depends on Homeobox D10 and MicroRNA-7b Inhibiting GABBR1 Translation in Paraventricular Nucleus

Wang

Huang

Zhou

et al. 2016

Circ: Heart Failure

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“…AVP regulates urea movement in the epithelium of terminal inner medullary collecting duct of the kidney and maintains osmotic equilibrium to prevent osmotic diuresis [16]. However, the role of renal medullary hyaluronan and urea transport mechanism in heart failure is not known [17]. It has also been speculated that AVP produces natriuretic effect by stimulation of oxytocin receptors in the renal medullary collecting ducts, possibly attributed to the structural similarities between neurohypophysial hormones [18].…”

Section: Pathophysiology Of Avp In Heart Failurementioning

confidence: 99%

Cardiorenal Syndrome: Role of Arginine Vasopressin and Vaptans in Heart Failure

et al. 2017

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Heart and kidney failure continued to be of increasing prevalence in today’s society, and their comorbidity has synergistic effect on the morbidity and mortality of patients. Cardiorenal syndrome (CRS) is a complex disease with multifactorial pathophysiology. Better understanding of this pathophysiological network is crucial for the successful intervention to prevent advancement of the disease process. One of the major factors in this process is neurohormonal activation, predominantly involving renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP). Heart failure causes reduced cardiac output/cardiac index (CO/CI) and fall in renal perfusion pressures resulting in activation of baroreceptors and RAAS, respectively. Activated baroreceptors and RAAS stimulate the release of AVP (non-osmotic pathway), which acts on V2 receptors located in the renal collecting ducts, causing fluid retention and deterioration of heart failure. Effective blockade of AVP action on V2 receptors has emerged as a potential treatment option in volume overload conditions especially in the setting of hyponatremia. Vasopressin receptor antagonists (VRAs), such as vaptans, are potent aquaretics causing electrolyte-free water diuresis without significant electrolyte abnormalities. Vaptans are useful in hypervolemic hyponatremic conditions like heart failure and liver cirrhosis, and euvolemic hyponatremic conditions like syndrome of inappropriate anti-diuretic hormone secretion. Tolvaptan and conivaptan are pharmaceutical agents that are available for the treatment of these conditions.

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“…Enhanced vasoconstrictive neurohormones are the shared pathways, such as the renin–angiotensin system components, vasopressin and catecholamine. These vasoconstrictive neurohormones are enhanced by arterial underfilling in both liver cirrhosis and heart failure . Inappropriate increases in these neurohormones result in renal ischemia, Na retention and the further induction of volume overload.…”

Section: Renal Injury In Liver Cirrhosis and Heart Failurementioning

confidence: 99%

Diuretic usage for protection against end‐organ damage in liver cirrhosis and heart failure

Mori

Ohsaki

Oba-Yabana

et al. 2016

Hepatology Research

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Volume overload is common in liver cirrhosis, heart failure, and chronic kidney disease, being an independent risk factor for mortality. Loop diuretics have been widely used for treating volume overload in these patients. However, there is a tendency to increase the dose of loop diuretics partly because of diuresis resistance. Neurohormonal factors are also enhanced in these patients, which play a role in volume overload and organ ischemia. Loop diuretics cannot improve neurohormonal factors and could result in end-organ damage. The water diuretic tolvaptan has been approved for use for volume overload in heart failure and liver cirrhosis. Despite causing similar increases in urine volume, its characteristics differ from those of loop diuretics. Renal blood flow is maintained with tolvaptan but decreased with furosemide in heart failure patients. Neurohormonal factors and blood pressure are not markedly altered by tolvaptan administration. It is expected that these mechanisms of tolvaptan can protect against worsening renal function by volume overload diseases compared with loop diuretics. It has also been reported that some patients do not respond well to tolvaptan. Loop diuretics and tolvaptan share the same mechanism with regard to decreasing renal interstitial osmolality, which plays a fundamental role in water diuresis. Thus, a high dose of loop diuretics could result in resistance to tolvaptan, so tolvaptan should be administered before increasing the loop diuretic dose. Therefore, volume control without enhancing end-organ damage can be achieved by adding tolvaptan to a tolerable dose of Na-sparing diuretics.

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Renal neurohormonal regulation in heart failure decompensation

Abstract: Jönsson S, Becirovic Agic M, Narfström F, Melville JM, Hultström M. Renal neurohormonal regulation in heart failure decompensation.

Cited by 36 publications

References 70 publications

Sympathoexcitation in Rats With Chronic Heart Failure Depends on Homeobox D10 and MicroRNA-7b Inhibiting GABBR1 Translation in Paraventricular Nucleus

Sympathoexcitation in Rats With Chronic Heart Failure Depends on Homeobox D10 and MicroRNA-7b Inhibiting GABBR1 Translation in Paraventricular Nucleus

Cardiorenal Syndrome: Role of Arginine Vasopressin and Vaptans in Heart Failure

Diuretic usage for protection against end‐organ damage in liver cirrhosis and heart failure

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