Arginine vasopressin (AVP) and treatment with arginine vasopressin receptor antagonists (vaptans) in congestive heart failure, liver cirrhosis and syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Gassanov, Natig; Semmo, Nasser; Semmo, Mariam; Nia, Amir M.; Fuhr, Uwe; Er, Fikret

doi:10.1007/s00228-011-1006-7

Cited by 41 publications

(28 citation statements)

References 75 publications

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“…Based on the well-known function of V 2 receptors in renal collecting duct aquaporin-2 mobilization, we suspect a renal-mediated mechanism is hyperactive in sRA mice, though we have not here directly examined the localization of the V 2 receptors responsible for the observed antihypertensive actions of tolvaptan. These data may support the use of the sRA mouse as an experimental model of the SIADH (18) or other diseases characterized by elevated AVP production or reduced clearance. The brain-specific generation and action of angiotensin peptides is gaining substantial interest for the regulation of cardiovascular function, fluid balance, metabolic control, and even learning and memory.…”

Section: Perspectives and Significancementioning

confidence: 80%

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Hypertension in mice with transgenic activation of the brain renin-angiotensin system is vasopressin dependent

Littlejohn¹,

Siel²,

Ketsawatsomkron³

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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An indispensable role for the brain renin-angiotensin system (RAS) has been documented in most experimental animal models of hypertension. To identify the specific efferent pathway activated by the brain RAS that mediates hypertension, we examined the hypothesis that elevated arginine vasopressin (AVP) release is necessary for hypertension in a double-transgenic model of brain-specific RAS hyperactivity (the "sRA" mouse model). sRA mice experience elevated brain RAS activity due to human angiotensinogen expression plus neuron-specific human renin expression. Total daily loss of the 4-kDa AVP prosegment (copeptin) into urine was grossly elevated (≥8-fold). Immunohistochemical staining for AVP was increased in the supraoptic nucleus of sRA mice (~2-fold), but no quantitative difference in the paraventricular nucleus was observed. Chronic subcutaneous infusion of a nonselective AVP receptor antagonist conivaptan (YM-087, Vaprisol, 22 ng/h) or the V(2)-selective antagonist tolvaptan (OPC-41061, 22 ng/h) resulted in normalization of the baseline (~15 mmHg) hypertension in sRA mice. Abdominal aortas and second-order mesenteric arteries displayed AVP-specific desensitization, with minor or no changes in responses to phenylephrine and endothelin-1. Mesenteric arteries exhibited substantial reductions in V(1A) receptor mRNA, but no significant changes in V(2) receptor expression in kidney were observed. Chronic tolvaptan infusion also normalized the (5 mmol/l) hyponatremia of sRA mice. Together, these data support a major role for vasopressin in the hypertension of mice with brain-specific hyperactivity of the RAS and suggest a primary role of V(2) receptors.

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Section: Perspectives and Significancementioning

confidence: 80%

“…2, E and F), and the normalization of baseline hyponatremia and hypocalcemia in this model (Table 4 and Fig. 5) that are typical of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (18).…”

Section: R824mentioning

confidence: 96%

Hypertension in mice with transgenic activation of the brain renin-angiotensin system is vasopressin dependent

Littlejohn¹,

Siel²,

Ketsawatsomkron³

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…This signaling pathway leads to vasoconstriction in vascular smooth muscle cells and to hypertrophy in the myocardium, again similarly to the α 1 ARs (Figure 1). Thus, vasopressin receptor antagonism poses as a possible therapeutic strategy in HF to combat cardiac hypertrophy, high blood pressure and systemic vascular resistance, overactivation of other cardiotoxic neurohormonal systems (eg, RAAS, SNS), and, of course, to reduce volume overload of the heart, along with its accompanying water and electrolyte abnormalities, which stem from the excessive V 2 R-dependent anti-diuresis in the kidneys that causes hyponatremia 74,75. Nevertheless, the main indication for vasopressin receptor antagonist drugs currently is hyponatremia (along with some other renal indications), and only in very few countries (eg, Japan but not in the USA) are they currently approved for congestive HF (Table 1).…”

Section: Targets For Hf Therapy In Signaling From Other Gpcrsmentioning

confidence: 99%

Current and future G protein-coupled receptor signaling targets for heart failure therapy

Siryk-Bathgate¹,

Dabul²,

Lymperopoulos³

2013

DDDT

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Although there have been significant advances in the therapy of heart failure in recent decades, such as the introduction of β-blockers and antagonists of the renin–angiotensin–aldosterone system, this devastating disease still carries tremendous morbidity and mortality in the western world. G protein-coupled receptors, such as β-adrenergic and angiotensin II receptors, located in the membranes of all three major cardiac cell types, ie, myocytes, fibroblasts, and endothelial cells, play crucial roles in regulation of cardiac function in health and disease. Their importance is reflected by the fact that, collectively, they represent the direct targets of over one-third of the currently approved cardiovascular drugs used in clinical practice. Over the past few decades, advances in elucidation of the signaling pathways they elicit, specifically in the heart, have led to identification of an increasing number of new molecular targets for heart failure therapy. Here, we review these possible targets for heart failure therapy that have emerged from studies of cardiac G protein-coupled receptor signaling in health and disease, with a particular focus on the main cardiac G protein-coupled receptor types, ie, the β-adrenergic and the angiotensin II type 1 receptors. We also highlight key issues that need to be addressed to improve the chances of success of novel therapies directed against these targets.

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“…Tolvaptan is a non‐peptide orally available arginine vasopressin V 2 receptor antagonist . The drug has been approved for the treatment of hyponatremia in the USA, for the treatment of hyponatremia secondary to syndrome of inappropriate antidiuretic hormone in the EU, and for the treatment of volume overload in patients with heart failure in Japan .…”

Section: Introductionmentioning

confidence: 99%

Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized, double‐blind, placebo‐controlled trial

Sakaida

Kawazoe

Kajimura

et al. 2013

Hepatology Research

129

176

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Arginine vasopressin (AVP) and treatment with arginine vasopressin receptor antagonists (vaptans) in congestive heart failure, liver cirrhosis and syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Cited by 41 publications

References 75 publications

Hypertension in mice with transgenic activation of the brain renin-angiotensin system is vasopressin dependent

Hypertension in mice with transgenic activation of the brain renin-angiotensin system is vasopressin dependent

Current and future G protein-coupled receptor signaling targets for heart failure therapy

Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized, double‐blind, placebo‐controlled trial

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