Hyponatremia and Vasopressin Antagonism in Congestive Heart Failure

Kumar, Siva; Rubin, Sharon; Mather, Paul; Whellan, David J.

doi:10.1002/clc.18

Cited by 24 publications

(12 citation statements)

References 30 publications

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“…The definition of the specific cut-off value of serum sodium varies in different trials because of the different study populations. [45][46][47] Through analysis, we found the optimal threshold of the serum sodium level was 136.6 mmol/L in our cohort, which was similar to the definition in the ACTIVCHF trial. 48) Kaplan-Meier analyses demonstrated reduced survival in patients with serum sodium higher than 136.6 mmo/L.…”

Section: Discussionsupporting

confidence: 76%

Predictors of Long-Term Mortality in Patients With Acute Heart Failure

et al. 2017

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SummaryTo investigate parameters which were related with long-term mortality in patients hospitalized for acute heart failure (AHF).A total of 287 patients with AHF presenting to the First Affiliated Hospital of Nanjing Medical University were enrolled into the registry from April 2012 to January 2015. The primary endpoint was all-cause mortality within 1 year; the association between variables and prognosis was assessed after 1 year.Among the 287 patients, 17 did not continue follow-up and 47 (17.4%) passed away. Baseline NT-proBNP and sST2 concentrations were higher amongst deceased than among survivors (P < 0.001). Serum sodium concentrations of patients who died were lower (P < 0.001). In receiver operator characteristics (ROC) analyses, the area under the curve (AUC) values for NT-proBNP, sST2, and serum sodium to predict 1-year mortality were 0.699 (95%CI 0.639-0.755), 0.692, (95%CI 0.634-0.747), and 0.694 (95%CI 0.634-0.750), respectively. The optimal cut-off points for NT-proBNP, sST2, and serum sodium were 2137.0 ng/L, 35.711 ng/mL, and 136.6 mmol/L, respectively. In Cox regression analysis, ln-transformed NT-proBNP (HR 1.546, P = 0.039), ln-transformed sST2 (HR1.542, P = 0.049), and serum sodium (HR 0.880, P = 0.000) values reliably predicted long-term mortality after multivariable adjustment.In patients with acute heart failure, NT-proBNP, sST2 and serum sodium are potential predictors of 1-year mortality. (Int Heart J 2017; 58: 409-415)

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Section: Discussionsupporting

confidence: 76%

Predictors of Long-Term Mortality in Patients With Acute Heart Failure

et al. 2017

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“…RAAS is also known to be inappropriately elevated among heart failure patients. 13) RAAS activation triggers hypokalemia in the tubules of the kidney, which is one of the causes of the secondary renal diabetes insipidus. It was reported that hypokalemia caused a reduction in the intracellular level of cAMP (cyclic adenosine monophosphate), which acts as the secondary messenger of AVP, and downregulated aquaporin-2 in the collecting duct.…”

Section: Article P461mentioning

confidence: 99%

Predictors for Tolvaptan Treatment and Future Perspectives

Nitta

2016

Int. Heart J.

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H eart failure is a major cause of morbidity and mortality worldwide which poses a great burden not only on the patient but also society owing to its expensive health-care related costs.1) During the past 2 decades, the medication strategies for heart failure have progressed significantly like β-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and aldosterone blockers. Although these drugs have somewhat improved the prognosis of heart failure patients, there still remain many patients who suffer from congestive symptoms due to heart failure in spite of high dose diuretics. Tolvaptan (TLV), a unique drug with characteristics of aquaresis via its vasopressin type 2 (V2) receptor blockade,2) is a new drug which was manufactured originally in Japan for heart failure patients. TLV is a promising drug due to its low stimulation of the renin-angiotensin-aldosterone system (RAAS), and prevention of worsening renal function (WRF) and electrolyte balance abnormalities like hyponatremia and hypokalemia.3) Recently, many novel perspectives about the response to and TLV long-term effects of TLV in heart failure have been reported. [4][5][6] Among them, Kadota, et al reported new insights into predictors of a response to TLV by using the arginine-vasopressin (AVP)/plasma aldosterone concentration (PAC) ratio.7) This study was prospectively performed among 26 patients with decompensated heart failure who were treated with 15 mg of TLV. They investigated the effects of TLV on the RAAS and predictors for the response to TLV treatment by using multiple laboratory factors such as plasma renin activity, aldosterone concentration, AVP, and urine osmolality.TLV increased urine volume and decreased weight without WRF and caused no significant changes in the plasma renin activity or aldosterone concentration. The AVP/PAC ratio before TLV administration was positively correlated with urine volume and they reported the usefulness of the AVP/PAC ratio for predicting the TLV response. Although their study contains some limitations, it provokes important perspectives about prediction of the response to TLV and future challenges in the application of this promising drug. Article p.461Arginine-vasopressin (AVP) is synthesized in the supraoptic and paraventricular nuclei of the hypothalamus and released depending on hyperosmolarity or effective circulation volume loss. Non-osmotic stimulation of AVP is observed, especially among heart failure patients. It was reported that the severity of HF positively correlates with plasma AVP concentration 8) and higher AVP is related to a worse outcome. TLV inhibits AVP connection to V2 receptors in the renal collecting ducts and reduces water re-absorption via aquaporin-2 as a consequence. This aquaresis mechanism has many advantages compared to conventional loop diuretics. Loop diuretics are known for their activation of RAAS and decrease the glomerular filtration ratio and activation of the sympathetic nervous system by reducing the effective circulation volume via s...

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“…Physiologically, hyperosmolality increases, whereas hypoosmolality decreases plasma AVP concentration (4). However, in diverse pathological syndromes, such as hepatic cirrhosis (35), congestive heart failure (37,38), and nephrogenic syndrome (23,26,48), a decrease in osmolality fails to inhibit AVP release. This AVP release leads to water retention and contributes to the morbidity and mortality associated with these diseases (1, 22, 24, 37, 38).…”

Section: R952 Ang II Induces Trpv4 Trafficking In 4b Cellsmentioning

confidence: 99%

Angiotensin II induces membrane trafficking of natively expressed transient receptor potential vanilloid type 4 channels in hypothalamic 4B cells

Saxena

Bachelor

Park

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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We previously reported that in the rodent, a model of dilutional hyponatremia associated with hepatic cirrhosis, TRPV4 expression is increased in lipid rafts from the hypothalamus and that this effect may be angiotensin dependent. In this study, we utilized the immortalized neuroendocrine rat hypothalamic 4B cell line to more directly test the effects of angiotensin II (ANG II) on TRPV4 expression and function. Our results demonstrate the expression of corticotropin-releasing factor (CRF) transcripts, for sex-determining region Y (SRY) (male genotype), arginine vasopressin (AVP), TRPV4, and ANG II type 1a and 1b receptor in 4B cells. After a 1-h incubation in ANG II (100 nM), 4B cells showed increased TRPV4 abundance in the plasma membrane fraction, and this effect was prevented by the ANG II type 1 receptor antagonist losartan (1 M) and by a Src kinase inhibitor PP2 (10 M). Ratiometric calcium imaging experiments demonstrated that ANG II incubation potentiated TRPV4 agonist (GSK 1016790A, 20 nM)-induced calcium influx (control 18.4 Ϯ 2.8% n ϭ 5 and ANG II 80.5 Ϯ 2.4% n ϭ 5). This ANG II-induced increase in calcium influx was also blocked by 1 M losartan and 10 M PP2 (losartan 26.4 Ϯ 3.8% n ϭ 5 and PP2 19.7 Ϯ 3.9% n ϭ 5). Our data suggests that ANG II can increase TRPV4 channel membrane expression in 4B cells through its action on AT1R involving a Src kinase pathway.angiotensin; TRPV4; hypothalamus; 4B; SRC kinase; SRY TRANSIENT RECEPTOR POTENTIAL (TRP) channel superfamily plays a central role in sensory physiology (47, 54). The TRP subfamily vanilloid member 4 (TRPV4) is a nonselective cation channel that is calcium permeable and shows polymodal activation by diverse stimuli including, but not limited to, moderate heat, cell swelling, and endogenous ligands (51,55,69). Functionally, it is strongly implicated in a number of physiological systems that include endothelial function and vascular tone (21, 64), renal function (56), central osmosensation (41, 46), and regulating hydromineral homeostasis (51, 55, 69). Mutations of TRPV4 are linked to a number of motor and sensory neuropathies and skeletal dysplasias (51, 69).TRPV4 is expressed in central nervous system (CNS) regions involved in neuroendocrine function including neurosecretory cells in the supraoptic nucleus (SON) and the paraventricular nuclei of the hypothalamus (PVN) (3, 9). In a rodent model of cirrhosis, we have previously reported increased TRPV4 trafficking to lipid rafts in hypothalamic samples that contained the SON, the PVN, and the organum vasculosum of the lamina terminalis (9). Importantly, we also found that increased TRPV4 trafficking correlated with activation of renin-angiotensin system (RAS) and was reversed after RAS inhibition (9).Angiotensin II (ANG II) is an effector molecule of RAS (25). Circulating ANG II is known to contribute to water and electrolyte homeostasis peripherally and centrally through its actions on blood-brain barrier-deficient circumventricular organs in the forebrain and dorsal hindbrain (31, 43). As part of the ...

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Hyponatremia and Vasopressin Antagonism in Congestive Heart Failure

Cited by 24 publications

References 30 publications

Predictors of Long-Term Mortality in Patients With Acute Heart Failure

Predictors of Long-Term Mortality in Patients With Acute Heart Failure

Predictors for Tolvaptan Treatment and Future Perspectives

Angiotensin II induces membrane trafficking of natively expressed transient receptor potential vanilloid type 4 channels in hypothalamic 4B cells

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